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From YouTube: DevoWorm #37: C. elegans multimodal integration/push-pull morphogenesis, shape and differentiation
Description
What's new in C. elegans: multimodal integration and its connection to mammalian forms of integration, push-pull morphogenesis in the developing gonad, shape changes and stem cell differentiation, update on Bacillaria image processing. Attendees: Richard Gordon, Bradly Alicea, Morgan Hough, Susan Crawford-Young, and Alon Samuel
A
B
You're
studying
it
and
they
can't
get
placental
material
to
be
white,
placental
material,
so
I'm
going
well.
They
need
to
look
at
it
from
a
physical
standpoint.
B
They
know
about
shear
shear
stress
in
vascular
cells,
so
they
have
a
clue
but
I
don't
know
they're
trying
to
collect
material
from
the
end
of
pregnancy.
For
this
yeah
and
maybe
it's
the
end
of
their
lifetime.
These
cells
they're
having
trouble
that's
what
the
email
was
about.
Yeah,
okay,.
A
I'll
have
to
check
into
that
in
the
origin
of
life's
literature,
because
you
know
there
there's
some
stuff
on
keratin
articles,
which
would
be
which
would
be
nanoparticles
with
getting
into
primitive
cells
or
or
protocells
things
before
those
life.
So
we
will
I'll
be
looking
into
that.
Okay,.
B
Okay,
yeah
well,
no
I
I
can
see
where
he
could
do
that.
It's
just.
A
B
B
A
B
A
B
A
A
A
C
C
Yeah
yeah
welcome
to
the
meeting
glad
to
see
everyone
here.
Dick
and
I
just
had
a
meeting
about
breast
cancer,
physics
and
interesting
topics.
There
a
lot
of
interesting
things
going
on
in
that
area,
so
yeah
other
than
that
I,
don't
know
if
people
have
updates
if
they
want
to
see
mention
anything
they've
seen
in
the
literature
recently
or
anything.
A
B
I
sort
of
have
I
sent
it
to
to
thick
and
should
I
try
to
refine
that
to
find
the
literature
behind
that
sheet
that
they
they
make.
B
Well,
there's
two
topics:
one
was
blood
cell
differentiation
and
in
one
case
they
got
long
thin
cells
and
large
flat
cells
when
they
added
a
cytokine
to
some
precursor
blood
cells.
So
that
was
interesting
because
they
got
both
cell
types
and
the
other
one
was
biomedical
engineering
lecture.
Where
there's
someone
in
Pharmacy
working
at
my
university
University
of
Manitoba,
that
is
working
on
nanoparticles
and
she's.
One
of
the
things
she's
looking
at
is
the
the
placental
barrier.
B
Yeah,
that's
the
more
interesting
one.
The
other
one
with
the
cytokine
is
just
like:
okay,
two
cell
types.
Why.
B
C
Yeah
that
sounds
great
yeah.
You
can
send
those
along
I'd
be
interested
to
see
them.
Okay,
so
yeah.
We
don't
really
have
anything
any
updates
on
the
projects.
So
we
still
have
a
lot
I'm
working
on
the
basil
area
stuff
and
we
have
we're
still
working
on
the
devograph
work
and
that's
coming
along,
but
nothing
to
report
on
that
right
now.
C
So,
let's
see
so
I'll
go
right
to
this
folder
of
papers
that
I
have
here
and
a
lot
of
interesting
things
going
on
this
week
with
respect
to
see
elegans
and
some
of
the
other
things
in
the
literature.
So
I
know
dick
sent
me
one
paper
on,
and
this
is
on
C
elegans.
C
So
there
are
actually
two
papers,
but
dick
sent
me
this
one
on
multi-sensory
processing
in
the
C
elegans
and
I
thought
that
was
interesting,
especially
with
respect
to
you
know
just
kind
of
broader
topics
and
what
they
call
multi-sensory
integration.
So
this
is
a
review
article
from
the
journal
brain
sciences
and
they
have
it's
called
multi-sensor
integration
and
c
elegans
and
comparison
to
mammals.
So
they
do
and
it's
a
it's
a
pretty
broad
comparison,
because
C
elegans
is
far
much
much
different
than
mammals
in
terms
of
the
way.
C
Work
and
that
so,
but
but
anyways
they
make
this
connection
and
I
find
it
interesting.
So
let
me
zoom
into
the
abstract
here,
so
this
is
from
a
Chinese
group
here
and
they're
abstract
reads:
multi-sensory
integration
refers
to
sensory
inputs
from
different
sensory
modalities
being
processed
simultaneously
to
produce
a
unitary
output.
C
So
what
they
mean
by
that
is
that
you
have
signals
from
different
sources
and
they're
coming
into
a
single
like
integrator,
neuron
of
some
type
and
then
C
elegans,
it's
usually
some
sort
of
interneuron,
and
then
the
interneuron
puts
out
a
signal
that
integrates
those
senses.
C
So,
for
example,
you
can
have
and
see
elegans
you
can
have
a
touch
sensor
and
a
chemical
sensor
and
those
two
things
can
come
together
in
an
in
and
feed
into
an
inner
neuron,
and
then
the
inner
neuron
is
producing
a
signal
that
is,
you
know,
producing
what's
integrated
from
that
multi-sensor
integration
is
known.
For
being.
C
You
know
for
sort
of
sort
of
having
the
super
additive
capacity,
meaning
that
it's
you
know
you
can
add
the
two
together
and
you
can
get
a
result,
but
what
really
makes
multi-sensor
integration
special
is
that
you
can
have
the
super
additive
effect.
So
you
can
have
you
know
if
you
were
just
to
add
in
like
your
your
chemical
sensing,
with
your
touch
sensing
that
would
give
you
you
know
sort
of
those
two
things
overlapping,
but
in
multi-sensor
integration
it
actually
increases
the
amount
of
information
that
you
have
in
a
super
linear
fashion.
C
So
that's
that's
what
they're?
That's
why
it's
special
and
that's
why
they
refer
to
it
as
multi-sensor
integration.
As
for,
like
you
know,
in
in
mammals,
we,
you
know
kind
of
think
of
this
as
sort
of
risk
for
higher
level
cognition,
so
higher
level.
Cognition
being
you
know,
like
awareness
or
you
know,
being
able
to
to
put
information
together
in
in
different
ways,
see
elegans.
It's
not
clear
at
see.
C
But
if
you
think
of
these
circles
as
brain
regions
instead
of
individual
neurons,
then
that's
basically
what
happens
in
mammals.
So
in
C
elegans
you
have
these
Sensory
neurons,
which
are
established
on
the
outside
of
the
body,
so
they're
interfacing
with
the
environment
and
they're
sensing
all
different
types
of
things.
So,
as
we
mentioned
in
the
from
that
paper,
they
give
a
lot
of
examples
of
this.
C
And
so
since
things
are
bilateral
and
C
elegans
as
they
are
mammals,
we
have
one
on
each
side.
So
we
have
these
three
hypothetical
Sensory
neurons,
the
three
and
you
know
the
projector,
their
corresponding
and
turn
around.
So
these
interneurons
then
are
processing
this
information
they're,
taking
in
information
from
the
X
from
the
periphery
and
they're
moving
it
Forward
into
the
central
part
of
the
connectome.
C
Now
in
the
paper
they
mentioned
that
there's
a
synaptic
postsynaptic
modification
here,
potentially
the
happens
to
modify
what
goes
on
in
in
the
interneuron.
But
the
interneuron's
main
role
is
to
integrate
this
information
and
give
an
output.
So
the
output
is
going
to
be
some
sort
of
mathematical
function
in
mammalian,
multi-sensor
integration.
If
you
read
a
lot
of
the
stuff
by
Stein,
you
know
Barry
Stein
and
some
of
his
colleagues.
C
They
talk
about
this
they're
different
mathematical
models
for
this
there's
Ernst,
who
talks
about
this
in
terms
Bayesian
models,
so
there's
a
Bayesian
function
that
one
can
use.
You
can
also
use
other
types
of
models,
but
this
idea
that
there's
a
super
additivity.
So,
let's,
let's
use
a
sort
of
a
simple
numeric
example.
So
say
the
level
of
input
here
is
a
2
and
this
sensory
neuron
and
the
level
of
input
in
the
sensory
neuron
is
a
five.
C
C
So,
instead
of
a
seven,
we
would
have
a
10,
maybe-
and
it's
just
basically
a
super
additive
result.
Maybe
you
know
you
have
things
like
that.
The
information
is
concurrent,
it's
amplifying
itself
or
that
the
information
is
different
enough
so
that
it
creates
it
generates
new
information.
So,
for
example,
if
you
have
a
vibration-
and
you
have
a
chemical
stimulus,
those
things
can
be
put
together
in
a
certain
way,
so
that
it
creates
new
information.
And
so
this
is
super
additive
and
when
they
talk
about
superactivity,
it's
usually
something
about.
C
It's
some
sort
of
electrical
response,
so
they
can
actually
measure
it
neurophysiologically.
So
this
is
this
is
super
additivity
you
can
have
additivity.
You
can
have
super
additivity.
You
can
also
have
sub-additivity
where
different
pieces
of
information
suppress
each
other.
Sometimes
it
becomes
less
clear
when
you
have
two
sources
of
sensory
information,
what
the
actual
output
should
be,
and
so
that's
where
you
have
subatitivity
and
again
that
would
be
in
this
case,
where
you
would
have.
This
would
add
up
to
seven.
C
So
that's
the
unitary
output
that
they're
talking
about
surrounded
by
stimuli
from
multiple
modalities,
animals
use
multi-sensor
integration
to
form
a
coherent
and
robust
representation
of
the
complex
environment.
So
again
they
use
this.
They
build
this
representation
of
their
environment.
They
have
to
figure
out
where
say
their
food
source
is
maybe
where
predators
are,
and
they
can.
You
know,
build
a
map
of
that
in
their
in
their
brains
and
so
that's
what
they
mean
by
representation,
even
though
the
multi-sensor
integration
is
fundamentally
essential
to
animal
life.
C
Our
understanding
of
the
underlying
mechanisms,
especially
at
the
molecular
synaptic
in
circuit
levels
or
means
poorly
understood,
the
study
of
of
sensory
perception
and
C
elegans
has
begun
to
fill
this
Gap,
so
people,
you
know
when
we
do
things
in
open
worm,
we're
modeling
a
number
of
circuits
that
involve
sensing
and
other
types
of
things.
C
We
have
gained
a
considerable
amount
of
insight
into
the
general
principles
of
sensory
neurobiology
owing
to
see
elegans
highly
sensitive
perceptions,
so
they
have
a
pretty
good,
like
you
know,
we're
talking
about
Tetra
receptors,
chemical
receptors.
You
know
things
like
that,
but
they're
very
high
resolution.
It's
not
like
they're,
just
these
primitive
things,
they're
very
you
know
robust
in
and
of
themselves,
relatively
simple,
it's
a
relatively
simple
nervous
system,
but
we
have
a
lot
of
genetic
tools
that
we
can
use
to
get
at
some
of
these
mechanisms
in
the
cells.
C
C
Yes,
so
we
we've
gained
a
considerable
amount
of
insight
into
the
general
principles.
The
sensory
neurobiology,
going
to
see
Elegance
highly
sensitive
perceptions,
relatively
simple
nervous
system.
Many
interesting
paradigms
of
multi-sensor
integration
have
been
characterized
in
the
C
elegans,
for
which
input
convergence
occurs
at
the
sensory
neuron
or
the
interneuron
level,
and
this
narrative
review
We
describe
some
representative
cases.
A
multi-sensor
integration
in
C
elegans,
summarize
the
underlying
mechanisms
and
compare
those
with
mammalian
systems.
C
So
if
we
go
down
to
the
examples
here,
so
it's
a
little
bit
different
than
what
you
might
find
in
mammals,
I
guess
so.
The
first
one
is
sensory
processing
and
see.
Elegans
C
elegans
is
about
60
Sensory
neurons.
That
can
sense.
A
variety
of
sensory
modalities,
including
smell
taste,
touch
temperature,
light,
color
oxygen,
CO2,
humidity,
proprioception,
which
is
like
touch,
but
also
bodily
awareness,
where
the
organism
is
in
space,
magnetic
field
and
sound,
so
there's
a
actually
a
larger
class
than
I
mentioned
previously.
These
are
all
you
know.
C
A
A
Inside
the
notice
magnetic
field
does
this
mean
c
elegans
contains
little
particles
of
iron,
the
waste
of
birds
do.
C
I'm
not
sure
about
that,
but
I
know
that
I've
read
a
couple
papers
where
they've
talked
about
like
how
they
can
sense
magnetic
fields.
So
they
have
I,
don't
know
what
the
mechanism
is,
but
they
actually
it's
like
kind
of
almost
like
birds,
how
they
can
sense
magnetic.
B
Yeah,
that's
true
and
there's
more
work
on
robson's
or
like
in
our
eyes.
There's
that
change
with
Magnetic
options;
I'm
not
pronouncing
it
right,
but
anyway,
yeah.
C
C
The
yeah,
the
the
point
is,
is
that
there's
a
lot
of
different
things
that
it's
sensing
and
it's
interesting
that
we've
been
talking
about
diatoms
and
we
just
put
this
paper
out.
It's
going
to
be
coming
out
in
a
book
chapter
soon,
where
we
talk
about
some
of
these
sensory
modalities
in
diatoms,
so
diatoms
you
have
since
Sensory
neurons
or
you
don't
have
Sensory
neurons,
but
you
have
chemicals
or
you
have
sensor
sensors
in
the
cell.
C
C
C
Oh
yeah
I:
don't
think
they
have
a
gravity
sense
of
sense
of
gravity,
but
I
don't
know
if
that's
like,
maybe
something
that
they're
using
like
a
combination
or
proper
reception
and
position
or
what
but
okay.
Why
would
you
ask
that
I
mean
just
curious?
Oh.
C
But
yeah
there's
yeah,
so
it's
you
know
you
have
like
diatoms,
which
are
single
cell.
You
see
elegans,
which
is
very
simple.
A
very
simple
nervous
system
of
you
know
a
handful
of
cells
relative
to
the
mammalian
brain
which
has
a
lot
of
structures
and
when
we
sense
you
know
gravity
we
have
our.
We
do
this
with
an
organ,
a
vestibular
organ.
So
it's
you
know
it's
a,
but
you
can
do
these
things
as
simpler
mechanisms
and
so.
A
A
C
So
all
right
so
for
each
environmental
stimulus,
assayed
and
isolation,
the
fundamental
neural
circuit
is
well
characterized
in
the
corresponding
behavioral
output
is
generally
robust,
so
that
that
you
know
that
gives
you
this
idea
that
they're
the
single
modalities
that
get
processed
from
the
sort
of
the
sensory
neurons,
which
are
sort
of
the
outer
layer
of
the
organism,
then
you
have
these
interneurons,
which
are
what
those
neurons
feed
to
and
that's
where
we're
interested
in
this
integration.
So
we
have
sensory
processing.
C
We
have
these
different
protein
receptors
that
can
sense
stimuli,
so
this
of
the
neurons
actually
can
be
very
highly
specialized
in
different
ways,
and
it
depends
on
the
protein
receptors
on
the
cells.
So
you
know
it's
like
basically,
maybe
a
similar
mechanism
to
diatoms,
but
you
also
have
that
connected
to
a
network
of
cells,
and
you
usually
have
multiple
cells
that
can
sense.
C
You
know
the
environment
instead
of
just
doing
it
in
a
single
cell
and
then
it
kind
of
talks
about
signal,
transduction
and
theorganization
of
the
sensory
system
from
all
modalities
is
vastly
different
in
C
elegans,
compared
to
mammals
due
to
its
numerical
simplicity.
So
an
olfactory
sensation.
You
have
a
pair
of
three
three
different
class,
three
different
neurons,
so
AWA
AWB
and
AWC,
and
then
you
have
a
pair
of
each
of
those.
So
you
have
six
neurons
and
these
six
neurons
serve
as
the
primary
odorant
hemosensory
neurons.
C
So,
instead
of
having
a
nose,
C
elegans
has
six
neurons
that
do
this
odorant
sensation,
chemosensation
and
so
and
well.
Worms
are
likely
to
express
around
100
gpcrs,
which
are
these
protein
receptors
as
presumed
odor
receptors.
So
each
of
these
cells
they
have
each
I
guess
it's
in
each
cell.
They
have
about
a
hundred
or
across
the
cells
you
have
about
100
of
these
protein
receptors
expressed,
and
so
those
are
the
things
that
are
enabling
this
sensation.
C
C
C
They
have
this
olfactory
organ
that
Maps
odors
to
different
channels,
and
so
you
have
many
many
cells
in
this
olfactory
system
that
can
process
odors
and
it
can
be
highly
specific
and
C
elegans,
it's
less
specific
with
respect
to
the
mapping
of
single
cells,
but
you
can
sense
a
lot
of
things.
So
this
means
that
the
C
elegans
you
maybe
need
a
multi-sensory
integration,
even
more
so
yeah.
A
C
C
C
Yeah
I
might
do
that.
I,
don't
really
know
I,
don't
know
if
anyone's
done,
that
those
kind
of
experiments
where
they
look
at
different
odor
ends
and
see
which
one
I
mean
they're
different
types
of
bacteria.
I
guess
is
what
they're
you
know:
they're
they're
sensing
bacteria,
they're
sensing
other
types
of
maybe
a
biochemical
signals
from
other
organisms
and
those
things
might
be
highly
specific.
A
B
Oh
that's
interesting
for
a
robot
that
can
smell
its
way
around.
C
Well,
I
think
I
actually
remember.
People
were
doing
this
with
like
robots
where
they
would
like
sense,
different,
like
they
were
doing
like
chemical
detection,
or
you
know
like.
If
you
want
to
keep
you
want
to
make
sure
that,
like
a
place
is
safe,
that's
not,
chemicals
are
like
you
know,
going
to
kill
people
or
whatever
can
sense
chemicals
in
different
ways.
B
C
C
So
so
the
the
point-
I
guess
the
other
connection
they're
making
here-
is
that
inner
neurons
comprise
the
largest
group
of
neurons,
which
is
probably
the
counterpart
of
higher
brain
regions
than
mammals,
so
those
these
Sensory
neurons.
They
send
their
information
to
these
interneurons,
where
this
is
where
you
get
this
integration.
C
So
it's
not
clear
what
they're
doing
exactly
with
respect
to
the
combinatorics,
but
the
combinatorics
are
going
to
be
sort
of
the
things
that
are
maybe
important
that
you
sense,
maybe
with
vibrational
stimuli,
can
be
integrated
and
made
more
important
so
like
if
you're
facing
some
predator
and
C
elegans
do
have
predators
or
you're
facing
some.
You
know
maybe
Big
Rich
vein
of
bacteria
bacterial
food-
you
can,
you
know,
encounter
it
and
engage
with
it
or,
if
you're.
Conversely,
if
it's
toxic
bacteria,
you
know,
then
you
can
back
away
from
it.
C
So
there
are
all
these
different
they're
different
signals
that
they
can
use
and
integrate
them,
and
so
they
talk
about
the
interneurons
being
divided
into
a
first
layer.
Second
layer,
Commander,
interneurons,
so
they're
different
types
of
interneurons
that
exist
in
C
elegans.
C
It's
a
very
important.
It's
just
part
of
the
connectome
in
general.
There
are
a
lot
of
different
types
of
inner
neurons
that
do
different
things.
So
I
don't
want
to
make
this
sound
like
they're
generic
inner
neurons.
They
do
a
lot
of
different
things
and
then
Sensory
neurons
projected
different
layers
of
interneurons
and
converge
into
five
Commander
interneurons,
that
control
muscle
movement.
So
there's
an
immediate
mapping
between,
like
the
sensory
inputs,
the
inner
neurons,
maybe
another
layer
of
neurons
and
then
the
muscles,
and
so
this
is,
you
know,
a
very
simple
circuit.
C
In
terms
of
the
connectome
they
they
emerge
at
different
times,
I
think
the
interneurons
kind
of
come
on
later.
So
you
get
certain
I
can't
remember
the
sequence
of
events,
but
I
think
that
yeah
they
get
wired,
they
get
wired,
I,
guess
sequentially
so,
but
they
don't
really
start
to
do
anything
until
after
hatch,
so
the
most
of
the
connector
was
wired
up
by
the
time.
They
actually
do
anything
like
this.
C
Don't
think
so,
I
think
a
lot
of
the
connections
are
really
going
to
be
post
hatch
I
mean
at
least
in
the
way
the
connectome
works.
If
we
were
to
compare
with
an
adult
connectome.
C
C
Yeah
well
we're
just
going
through
these
papers
on
C
elegans,
so
we're
going
through
this
paper
and
multi-sensory
integration
and
see
elegans
so
they'll
see
elegans,
performs
multi-sensor
integration.
C
There's
integration
at
the
level
of
sensory,
neurons
and
again
you'd
have
to
get
into
a
lot
of
the
details
of
different
neurons.
So
in
C
elegans
you
have
a
nomenclature
of
different
neurons.
You
know
you
have
like
they'll,
give
you
a
series
of
letters
here
at
Ash
and
that
actually
has
a
very
specific
function
in
every
C
elegans.
So
it's
not
like
the
mammalian
nervous
system
where
you
can
have
elasticity
and
the
cells
kind
of
proliferate
and
act
as
a
population.
C
These
circuits
are
very
specific
to
certain
neurons,
so
the
for
example,
the
ash
neuron
pair
is
the
main
nose
receptor,
sensory
neuron,
which
mediates
avoidance,
responses
and
noxious
stimuli.
So
you
know
it's
one
of
these
things
that
if
I
encounter
something
that's
noxious,
I
avoid
it.
So
that
might
mean
backing
up,
or
that
might
mean
moving
my
trajectory.
So
you
can
see
how
the
ash
neuronism
important
in
kind
of
directing
the
muscle
to
do
certain
things.
But
many
Sensory
neurons
are
polynomial,
which
meaning
means
that
they
can
sense
an
array
of
averse
of
cues.
C
So
they
can,
you
know,
sense
all
sorts
of
different
types
of
cues
like
nose
touches
if
you
take
like
a
what
they
call
worm
pick
and
you
tap
a
worm
on
the
nose.
It'll
move
back,
they're,
repellent
chemicals,
of
course,
and
other
types
of
things
that
they
sense
in
the
soil
when
they're
living
in
the
soil,
and
so
but
interestingly,
after
Ash
activation
C
elegans
can
separately
process
stimuli
from
different
modalities
by
innovating
different
Downstream
postsynaptic
receptors.
C
So
they
actually
have
these
mechanisms
postsynaptically,
meaning
that
the
cell
sends
things
down
to
the
synapse
and
then
their
postsynaptic
receptors
that,
yes,
that
play
a
role
in
what
information
gets
transmitted
to
the
negative
neuron.
So
this
is
another
level
of
processing
which
is
specific.
You
know
it
can
be
specific
to
different
things.
C
So
this
is
a
figure
here
showing
this.
These
poly
modal
neurons,
skimmy
away
from
different
modalities,
polymodal,
sensory,
neuron
and
then
there's
an
output
to
behaviors
in
B.
You
have
a
hub
and
spoke
circuit,
so
this
is
a
different
type
of
circuit,
where
you
have
different
things
in
the
environment
that
are
being
sensed
they're,
being
integrated
into
an
interneuron,
and
this
might
have
an
effect
on
social
behavior,
aggregation
of
worms
into
groups.
C
And
then
you
have
this
third
one,
which
is
a
two-circuit
layer,
which
is
where
you
have
these
outer
neurons,
which
sense
different
things
like
odor,
odorants
and
amino
acids
and
touch
they
get
integrated
into
these
different
neurons,
and
then
it
gets
integrated
here
into
this
black
box
and
then
there's
foraging
Behavior.
So
you
can
see
that
even
though
you
have
you
know
these
highly
specific
cells
and
circuits
and
then
about
300
neurons
total
on
the
connectome
that
they
do
a
lot
of
different.
There
are
a
lot
of
different
ways.
C
You
can
process
information,
so
this
is
not
like
as
complex
as
the
mammalian
brain,
but
it's
certainly
you
know,
has
some
similarities,
so
they
offer
this
table
where
they
talk
about
the
different.
You
know
the
dominant
modality
receptor
expression,
valiances
valence
of
stimulus,
which
is
where
they
just
talk
about.
Like
you
know,
what
is
the
stimulus,
positive
or
negative
for
the
organism?
C
The
common
method
of
measuring
neural
activity,
type
of
neuron
membrane
potential.
So
there
are
these
differences.
C
elegans
is
a
graded
potential,
whereas
mammals
have
an
actions
potential.
You
know
there
are
things
that
are
determined
that
in
C
elegans,
it's
mostly
neuron
by
neuron,
but
in
mammals,
it's
usually
in
a
brain
region.
C
C
So
this
kind
of
points
to
these
kind
of,
like
maybe
fundamental
aspects
of
sensory
repair
of
multimodal
integration
that
you
might
be
able
to
use
for
like
a
robot
or
something
but
they're
like
they're
sort
of
principles
that
can
be
extracted
here,
I'm,
not
sure
they
get
there
all
the
way
in
this
paper,
but
so
yeah,
okay,.
A
Great
question
are
the
sensory
neurons,
distributed
over
the
whole
surface
of
the
body.
C
I
think
in
different
yeah
on
the
outside
of
the
body,
like
you
know,
interfacing
with
the
environment,
but
they
have
them.
You
know
down
the
lateral
line,
I
believe
in
the
head,
and
maybe
some
in
the
tail.
Oh
yeah.
C
Well,
yeah,
they
do
have
a
lateral
line.
It's
a.
They
have
seen
cells
along
the
lateral
line.
I,
don't
know
if
it
acts
like
fish
but
like
they
definitely
have
that
lateral
line
system
of
okay.
D
C
So
and
see,
elegans
connect
the
movement,
especially
with
respect
to
movement.
The
circuits
are
actually
pretty
well
characterized
with
in
open
worm.
You
know
we
look
at
some
of
the
circuits
in
terms
of
movement.
You
can
observe
movements,
for
example
like
Omega
turns
which
are
like
where
they
turn
like
this,
or
they
back
up
sometimes,
and
those
things
are
very
stereotypical.
So
there
are
certain
circuits
that
produce
different
outputs
like
that.
C
Now
the
senses,
the
the
sensory
information
drives
that
the
state
of
that
surface,
so
it
might
be
an
inhibitory
it
might
be
enabling,
but
you
know
there,
so
we
know
about
what
a
lot
of
the
circuits
look
like,
but
it's
actually
quite
complex
as
to
their
operation.
So,
like
you,
can
look
at
like
connections
between
cells
and
the
activity,
but
also
like.
What's
the
cells
are
expressing
in
here
is
a
protein
receptors
and.
B
C
Channels
and
other
things
that
can
really
kind
of
mediate
some
of
these
movements.
So
it's
a
very
interesting
area.
We
have
some
things
in
open
where
my
channel
worm
and
some
of
the
other,
the
movement
project
that
we
do
so
if
you
looked
around
the
slack
you'll,
see
references
to
these
and
I
think
even
in
in
one
of
our
in
the
one
review
paper
we
had
in
2018,
we
talked
about
some
of
these
initiatives
so.
C
Of
C
elegans
Labs
too,
looking
at
this
sort
of
thing,
like
you
know,
movement
circuits
looking
at
how
they're
the
biology,
but
also
how
you
might
model
them
to
build
robots,
so
they're
Eduardo
was
scaredo
and
his
team
are
looking
at
that
how
to
map
that
to
robots,
and
so
it's
all
very
interesting
because
it's
a
very
simple
nervous
system,
but
it
has
a
lot
of
real.
You
know
potential
to
understand
a
lot
of
these
behaviors.
C
So
the
other
paper
new
paper
and
see
elegans
land
here
is
this
paper.
I
found
it's
recent.
It's
on
worm
development,
it's
on
gonad
morphogenesis,
which
sounds
really
exciting,
but
it's
actually
it's.
This
idea.
We've
talked
about
in
past
meetings
on
push-promorphogenesis,
so
it's
where
you
have
this
sort
of
buckling
of
epidermal
cells
and
they
form
like
patterns.
So
you
can
have
buckling
of
an
epidermal
layer
of
cells
and
they
can
form
these.
C
Of
of
like
stipple
patterns
or
like
grooves,
or
something
like
that,
and
so
the
idea
is
that
they're
pushing
on
each
other.
Their
forces
involved,
there's
also
a
gene
expression
in
the
cells
and
it's
it's
sort
of
enabling
this
more
physical
interaction
between
the
cells
and
this
sort
of
trans
transformation.
So
it's
a
kind
of
an
interesting
way.
You
know
it's
not
like
Turing
chemical
morphogenesis.
It's
not
exactly
like
the
standard
morphogenesis
that
we
think
about
it's
a
it's
a
different,
a
little
bit
different
mechanism
for
pattern
formation.
C
So
in
this,
in
this
case,
though,
they're
saying
that
push
not
pull
is
responsible
for
bonead
morphogenesis
so
and
see
all
against.
The
gonads
are,
of
course,
important
for
reproduction.
There's
a
there's,
a
germ
line,
so
the
cells
that
form
the
germ
line
separate
out
from
in
the
embryo.
Quite
early,
you
get
P
sub
lineage,
which
is
like
present
at
the
eight
I,
think
the
four
cell
stage,
and
that
P
lineage
becomes
isolated
from
the
rest
of
the
organism
and
the
reason
it
does.
C
That
is
because
you
needs
to
be
protected
from
somatic
mutations,
which
accumulates
as
the
organism
is
in
its
environment
and
and
accumulating
mutations.
So
there
that
happens
in
most
organisms
with
a
germline
where
the
mutation
you
know
it's
protected
from
mutations,
so
it
can
pass
on
its
genetic
material
to
its
Offspring.
Without
accumulating
a
lot
of
mutations,
I
mean
it
will
accumulate
mutations,
anyways,
but
they're
sort
of
germline
mutations,
which
are
a
bit
different.
C
So
the
question
is:
how
did
how
does
tissue
elongation
occur?
It's
a
recent
paper
identifies
a
new
mechanism,
the
elongation
of
the
C
elegans
from
Aphrodite
gonad,
and
this
is
driven
by
pressure
from
proliferating,
germ
cells
confined
within
a
tube,
so
there's
a
tube
that
that
gonador
morphogenesis
occurs
in
this
tube
then
has
these
germ
cells
in
it
and
those
germ
cells
proliferate,
The
Divide?
C
So
this
I
think
we
talked
a
little
bit
about
this
before,
but
this
is
another
example
of
what
this
firm
Aphrodite
going
at
elongation
looks
like
so
you
have
these
germ
cells
in
a
tube
here,
and
this
L2
is
the
developmental
stage.
This
is
post
hatch.
This
is
the
second
larval
stage,
which
is
a
pretty
early
in
C
elegans
development,
and
you
get
these
oocytes
that
form
germ
cells
later
on,
and
then
these
oocytes
get
sort
of
packed
in
this
tube
and
then
around
L3
they
become
smaller.
C
C
So
this
is
how
the
I
think
we've
seen
this
before,
where
there's
there's
this
curvature
in
the
morphogenesis
of
this
tube
in
the
gonad,
and
then
this
is
a
pump,
so
there's
a
pump
mechanism
that
drives
this
forward
so.
A
C
Let's
see
not
sure
that
well
I
think
the
volume
increases,
but
the
number
of
Celsius
increases.
So
it
looks
like
this
pump
is
important
here,
where
it's
it's
pushing
it
out
of
pressure
yeah.
C
So
it's
like
it's
like
a
balloon,
so
this
this
section
B
kind
of
it,
explains
it
a
little
bit
more.
So
you
have
this
curvature
and
you
have
this
pump,
which
is
pressure
from
proliferating,
germ
cells.
So
these
germ
cells
keep
dividing
and
they
build
up
pressure
at
this
thing
and
it
actually
pushes
this
tube
open.
So
it
pushes
it
forward
and
you
just
keep
getting
proliferation.
So
I
guess
there's
an
increase
in
volume,
but
there's
also
an
increase
in
the
number
of
cells
and
the
pressure
in
this
part
of.
C
Not
sure
they
get
quantitative
measurements
of
it,
but
if
you're
just
putting
the
they're
just
kind
of
inferring.
This.
A
Yeah,
if
you
look
at
that,
it's
very
similar
to
god-shaped
bacteria
and
archaea,
for
which
there
are
published
models,
I'm,
not
very
familiar
with
them,
and
that
allows
you
to
individual
bacteria
than
a
rod.
Shape
might
be
worth
looking
into
yeah
yeah,
okay,
because
one
of
the
one
of
the
problems
here
is
how
you
know
if
I
blow
up
an
ordinary
glue
and
it's
a
sphere
right.
C
A
So
the
the
stress
patterns
of
the
sheath
May
determine
the
shape
right,
in
which
case
you're
in
for
personal
electron,
microscopy.
C
They
actually
mentioned
I
think
in
here
that
they're
they're
actin
molecules
that
actually
play
a
role
in
the
surface
of
this.
So
let's
see
so
okay,
so
the
new
model
is
that
the
DTC
promotes
germline
proliferation
and
determines
the
path
ahead
by
secreting
Matrix
male
metalloproteases,
when
it's
time
to
turn
the
DTC
polarizes,
its
Matrix
adhesions,
creating
torque
that
bends
the
gonad
arm.
And
then
this
is
where
you
get
the
elongation.
Now
it's
that
you
have
this.
C
You
have
meiosis
and
two
contractility
and
actin
polymerization,
suggesting
that
the
DTC
does
not
have
its
own
engine
and
is
propelled
another
way
so
the
surface
or
this
tube
is
actually
awake.
Has
special
properties
and
the
cells
are
sort
of
propelling
it
along.
So
they
actually
did
these
computer
simulations,
so
they
actually,
but
they
use
the
qualitative
physical
model,
meaning
that
they
kind
of
built
the
model
kind
of
with
these
properties,
and
then
they
simulated
it.
C
A
Okay,
now
there's
another
system
which
might
be
analogous,
which
is
What's
called
the
snake
gourd.
Oh
yeah,
okay,
that's
long
and
narrow
and
worked
on
my
sinat
back
I.
Think
in
the
1950s
showed
that
the
orientation
of
the
cells
in
the
snake
board
are
more
parallel
to
each
other
than
in
a
round
board.
A
C
A
So
unless
they
have
a
mechanism
of
measuring
the
pressure
I'm,
not
sure
this
is
a
believable
part
yeah.
The
other
thing
is:
if
something
bends
into
a
u-shape,
if
you
bend
the
balloon
into
a
U-shaped,
it'll
tend
to
straighten
out.
So
is
there
a
torque
straightening
out
the
thing
and
if,
if
there
is
what
keeps
it
from
acting
great
okay,
yeah.
B
Apparently,
when
you
align
cells
as
they
divide,
they
exert
quite
a
force.
I've.
B
B
They
say:
there's
about
400
Pico
Newtons
created
with
a
spindle
or
maybe
a
thousand
depending
a
thousand
people
Newtons,
that's
a
lot
compared
to
an
individual,
actin
molecule
or
microtubule,
because
they're
on
the
order
of
one
or
four
Pico
Newtons
and
it's
a
spindle
in
a
dividing
cell
is
or
like
400
to
a
thousand
piconewtons.
B
This
thing
yeah
and
also
on
the
FL,
a
a
m
meaning
slam
meeting
I,
don't
know
how
to
pronounce
that
they're
women
studying
cells
last
week
said
that
there
was
a
cell
division
orientation
of
tissue
elongation.
She
did
mention
it.
B
A
C
It's
sort
of
a
qualitative
model
and
then
they
build
this
copy.
You
know
this
simulation
that
kind
of
shows
how
this
works,
but
of
course
there
are
other
things
that
need
to
be
in
place.
So
this
is
one
of
these
current
biology
dispatches.
It
doesn't
provide
a
lot
of
deep
methods,
but
you
know
still
so
then
how
does
the
cell
turn
previous
research
suggests
that
integrins,
which
link
Integra
or
other
kinds
of
integrins,
which
will
link
them
to
act?
C
They
act
in
cytoskeleton
are
critical
for
the
dtcs
to
steer
the
gonad
through
its
terms,
so
they
still
don't
address
necessarily
how
the
gonad
turns.
But
there's
this
steering
mechanism
and
I
mean
you
know
how
necessarily
it
turns,
but
how
it
doesn't
straighten
out
and
I.
Imagine
I
I.
Remember
your
balloon
analogy:
I
can
visualize
that
balloons
kind
of
when
you
blow
them
up.
They
they
can
curve
and
then
just
pop
back
out
to
a
straight
line.
C
So
there
are
other
things
that
are
probably
involved
and
then
so
there
are
a
number
of
questions
that
come
out
of
this.
A
lot
of
this
is
structural
biology,
but
still
you
know
there
are
a
lot
of
questions
about
how
you
know,
cells
stop
migrating,
and
this
is
something
if
you
know
people
are
interested.
There's
a
lot
of
literature,
maybe
not
not
very
much
known
about
how
these
processes
stop.
You
know
how
do
you
end
up
with
a
certain
number
of
cells
and
then
that's
it?
What
are
those
mechanisms?
C
And-
and
there
are
a
lot
of
a
lot
of
work's-
been
done-
I'm
kind
of
like
you
know
this
sort
of
program,
so
you
know
that
there
are
a
certain
number
of
Divisions
that
happen
and
then
that's
it
and
it's
usually,
you
know
people
have
thought
well,
it's
some
sort
of
chemical
signal,
but
you
know
we
don't
really
know
exactly
what
the
mechanisms
are
in
some
of
these
systems
so
yeah.
This
is
a
nice
overview
here,
and
this
is
based
on
a
recent
paper.
C
So
this
paper
is
in
developmental
cell
from
Ronin,
zytobar
and
colleagues.
So
actually
I
don't
know,
let's
see
if
they
mention
it
here
in
one
okay
one.
So
this
is
directed
cell
Invasion
and
asymmetric
adhesion.
C
So
this
is
so
I
think
I,
don't
know
if
we
covered
this
one
last
week
or
not,
but
this
kind
of
goes
over
some
of
the
stuff.
C
Maybe
I,
but
maybe
what
we've
talked
about
in
the
other
meeting
so
last
week.
So
that's
because
that's
that's!
What's
going
on
in
the
world
of
Clans
I
just
wanted
to
go
over
those
papers
just
to
give
people
a
taste
to
that
so
I
know.
Elon
is
waiting.
I
wondered
if
he
had
any
updates
on
what
he's
doing.
D
D
D
Yeah,
so
I
kind
of
just
kind
of
like
did
everything
in
the
in
the
devlog
that
I
kind
of
like
kind
of
feel
like
producing
and.
D
Yeah
I
kind
of
like
there
were
some
tasks
that
we
talked
about.
D
Yes,
the
last
time
and
I
kind
of
finished
kind
of,
like
almost
like
everything,
so
I
transformed
like
to
the
scale
I
scaled,
the
pixels
into
and
last
time
I
was
ending,
with
kind
of
tracking
like
a
one
pixel
within
a
diatom
and
now
I
transformed
it
from
pixels
to
micrometers,
with
the
scale
that
Thomas
provided
me,
I
rotated
it
to
one
axis,
using
the
polar
coordinates
and
kind
of
taking
the
beginning
of
like
each
each
trajectory
and
producing
that
and
also
I
duplicated
it
to
more
than
one
tracker
to
kind
of
like
use
like
as
many
trackers
as
you
want
Within
within
a
DOT
thermolic
District
in
general,
and
let's
see,
if
I
have
some
pretty
sure
yeah
sharing
the
screen.
A
D
Yes,
so
here
I
kind
of
try
to
like
two
two
points
within
like
single
data
term
and
then
I
added
more
points
in
more
diatoms.
The
problem
was
that
I
can
kind
of,
like
maybe
fix
later,
that
once
one
tracker
point
is
kind
of
like
missing.
So,
for
example,
if
I'm
tracking,
like
a
point,
for
example
like
here
and
then
it
kind
of
reaches
the
end
of
the
screen,
and
then
it
does
that's
kind
of
understandable,
but
then,
like
I,
was
kind
of.
Like
writing.
D
A
I
can't
like
an
aggregation
like
just
a
simple
kind
of
glue
the
galactics
and
collects
all
the
points,
but
then,
like
once
a
single
tracker
died.
There's
got
a
problem
with
that
to
connect
like
which
points
and
like
in
the
different
trackers
like
once
you
go
up
down
from
like
nine
tracking
points
to
eight
yeah,
but
anyway,
I
kind
of
like
wrote
that
to
to
do
in
the
next.
D
So
one
thing
is
kind
of
like
just
to
do
like
something
if
a
Tracker
kind
of
goes
to
the
end
of
the
screen.
The
second
thing
is
to
if
I
want
to
do
it
like
more
fancy,
if
we
want
to
do
like
a
segmentation
tool
like
to
for
diatoms
and
then
and
then
produce
like
the
tracking
points
from
like
the
instant
segment,
a
ction
of
each
data,
but
that's
kind
of
like
a
try
that
I
did
with
the
notebook.
D
That's
already
there
with
the
segment
segmenting
data
terms,
and
you
can
see
that
it
didn't
produce
kind
of
like
maybe
like
so
much
of
good
results.
I
mean
some
of
them
like
just
like
trying
to
yeah
identify
like
different
segments,
but
I
was
thinking
like
from
that.
I
would
need
to
kind
of
maybe
train
it
a
bit
more
before
I'm
going
to
use
it
to
my
needs.
D
So
that's
kind
of
like
more
like
two
stuff
to
kind
of
like
to
maybe
like
further
on
like
if
you
would
want
to
like
pursue
it,
and
maybe
the
last
thing
is
just
to
arrange
everything
and
then
just
commit
it
and
send
also
like
Thomas
the
the
points,
the
tracking
points
within
different
videos.
If
he
wants
to
and
then
like
see,
if
we
kind
of
like
reproducing
results,.
C
D
Yeah,
so
to
be
honest,
I
don't
exactly
know
what
the
percentages
are.
I
just
I
just
use
the
notebook
of
the
instant
segmentation
from
the
project,
the
basilaria
project
as
a
folder
instance
limitation.
There
so
just
used
it
so
I
can
check
this
yeah.
C
But
I
didn't
know
where
you're
getting
your
algorithm
from
so
this
is
yeah.
This
is
a
the
algorithm
that
was
being
used
there
so
that
yeah
they
had
a
it's
going
to
be
accuracy
percent
accuracy
or
something
like
that.
But
okay.
D
Yeah
accuracy,
like
a
prediction
like
yeah,
maybe
like
how
kind
of
like
short,
if
the
algorithm
thinks
it
is
yeah.
C
Because
it's
really
matching
well,
it's
it's
not
matching
it's
it's
like
it
has
a
model
of
what
that
self
should
look
like
and
then
it
it's
trying
to
match
it
up.
And
of
course
you
know,
you
wouldn't
think,
there's
much
variation
because
the
cells
are
very
similar.
But
it's
you
know
it's
picking
things
up
according
to
its
orientation
and
then
you
know
how
it's
sliding
against
the
other
cells.
So
it's
really
kind
of
you
know
it's
not
entirely
sure
about.
You
know
whether
it's
a
match,
but
it
it's
giving
you
some
confidence
interval.
D
A
D
Yes,
so
I
can
I
can
track
like
several
ones
at
once,
like
if
I'm
kind
of
like
at
the
moment,
I'm
just
clicking
like
different
points
that
I
want
to
track
and
then
it
starts
and
then
we're
gonna
just
do
a
demo.
If
for
you,
while
we're
at
it,
just
a.
A
A
D
D
D
So
I
know
that
this
is
the
diatom
that
kind
of
comes
like
from
the
beginning
to
the
end
of
the
screen,
so
I
just
clicked
like
both
of
them
and
then
it
kind
of
produces
the
points
or
like
the
pixels
that
I
want
to
track
and
I
can
maybe
click
here
and
click
another
one
here
so
and
then
now
I'm
pressing
Q
just
to
collect
just
to
start
the
program,
the
tracking
program
and
there's
a
flag
saying
if
I
want
to
if
I
want
to
show
the
video.
D
So
let's
turn
into
true
and
again
I'm
kind
of
clicking
and
then
now
it's
gonna
show
the
video
Once
I'm
gonna
go
out
and
you
see
like
it's
tracking
and
then
like
just
exiting
once
the
video
is
over
and
then
the
results
are
saved
within
the
same
folder
of
the
of
the
movie.
So
we
can
also
see
different
tracks.
D
D
Yeah
yeah,
that's
the
direction,
that's
the
starting
point.
That's
the
end
point
like
for
each
track
like
give
me
the
circle
says
the
end.
C
I'm,
just
taking
a
phone
call
yeah.
This
is
this
is
interesting,
so
yeah
you're
able
to
do
multiple
cells
at
once.
That's
interesting!
So
that's
that's
kind
of
an
interesting
question
because
you
know,
especially
when
you
reach
the
end
of
like
the
when
it's
making
a
accordion
slide
sort
of
at
the
end,
where
it's
rebounding,
that
that
should
give
you
some
information
there
for
what
we're
trying
to
look
at
so
dick.
You
wanted
to
say
something.
A
No,
that
was
a
that
was
a
joke,
call
any
progress,
Along
on
getting
Thomas
to
calibrate
his
camera.
Yes,.
D
No
I
think
I
didn't
I,
didn't
contact
him.
Yet
so
I'm
gonna
finish
this
and
then
okay,
you
can
send
it
to
him.
Yeah.
A
Okay,
you
know
I
think
the
only
way
to
do
that
would
be
turning
the
Microsoft,
so
it's
horizontal
and
then
using
Stokes
Raw,
okay,
Chris
Stokes
law
is
the
only
thing
I
can
think
of
where
you
can
do
guaranteed
uniform
velocity.
A
Okay,
so
I
I
think
that's
gonna.
It
has
to
be
done
before
we
publish
this
because
it's
how
should
I
say
it's
proof
that
it's
not
an
instrumental
error
right.
D
Yeah,
okay,
I'm
kind
of
more
like
thinking
about
these
two
and
like
tracking
tracking,
like
passive
area
automatically
and
I,
was
kind
of
thinking.
Maybe
like
a
next
step
like
if
we
so
there's
this
type
of
guy
like
using
it
to
produce
like
this
smooth
movement.
Kind
of
like
what
do
you
say,
like
with
kind
of
like
first
like
saying
that
the
camera
is
what
the
cuterness
of
the
camera
and
specifying.
A
D
A
Like
another
way
to
do
it
without
turning
the
microscope,
if
you
put
water
under
a
cover
slip
on
a
microscope
slide
then-
and
you
don't
seal
the
edges,
it
will
slowly
evaporate.
A
A
Yeah,
okay,
so
this
is
another
another
way
to
handle
the
problem
you
can
tell
if
the
particles
are
moving
smoothly
or
not
as
the
water
evaporates.
D
Cool
and
and
another
way
that
I
felt
like
maybe
this
school
once
it's
gonna
go
with
the
oh
sorry.
If.
A
A
Much
better
okay,
so
you
get
this.
You
put.
A
cover
slip
is
a
very
thin
sheet
of
glass,
we'll
put
it
on
top
of
a
cover,
a
microscope
slide
with
water
in
it,
then
the
water
will
evaporate
slowly
and
if
there
are
particles
in
the
water,
you
could
watch
them.
Move
okay,.
A
Okay,
so
anyway
propose
it
to
him,
see
what
it
fixed,
yeah,
okay
and-
and
what
freaked
me
out
is
when
I
tried
that
with
a
the
first
Apple
camera
and
it
didn't
work,
it
was
jiggly,
it
jiggled
all
over
the
place.
A
D
I
just
wanted
to
like
one
thing
with
it
that
if
that's
gonna
be
like
I
kind
of
like
gonna
combine
with
like
the
instant
segmentation
for
diatoms.
That
can
be
an
automatic
tool
to
kind
of
track.
Him
like
just
like
that
atoms
like
within
every
maybe
like
just
like
movie
as
long
as
someone's
gonna,
maybe
like
train
like
how
did
that
homes
can
like
look
like
in
the
beginning
kind
of
seriously
like
like
a
few
diatoms
and
then
like.
D
A
Okay,
so
they
have
a
track:
oh
most
die
at
times,
I'm,
not
multile.
They
don't
don't
move.
D
D
Mean
like
it's
also
like
another
apartment,
to
train
a
moving
Parts.
As
long
as
you
just
like.
Tell
the
the
tracker
right
there,
because
just
just
like
a
series
of
photos
and
in.
D
A
C
I
would
like
to
review
an
extra
paper
and
I
think
it'll
have
a
lot
of
relevance
to
the
multi-sensor
integration
stuff
and
the
gonad
morphogenesis
stuff.
We
talked
about
and
see
elements.
This
paper
is
in
mammals,
but
it
should
give
you
a
good
idea
of
how
what
they
call
stem
cell
niches
work
and
how
those
work
in
Oregon
or
for
Genesis
as
well.
So
this
is
this
title
is
paper,
is
cellular
shape,
reinforces
Niche
to
stem
cell
signaling
in
the
small
intestine,
so
in
mammalian
cells
in
particular,
not
so
much
in
C
elegant
cells.
C
What
are
your
developmental
stem
cells
have
a
niche,
so
a
niche
is
kind
of
like
a
micro
environment
that
the
cells
exist
in,
and
you
have
a
small,
intestine
or
say
in
the
liver,
where
you
have
cells
around
you
that
are
of
a
certain
type,
their
liver-like
or
small,
intestine
like,
and
that
stem
cell
will
then
take
on
the
fate
of
its
neighbors
and
there's
a
chemical
milieu.
That's
kind
of
controlling
a
lot
of
this,
and
so
the
cells
will
take
on
the
fade.
C
If
you
took
the
stem
cell
out
of
that
environment
and
put
it
into
another
environment,
it
would
take
on
a
different
feed.
So
really
there's
a
reinforcement
of
the
feet
through
this
niche,
but
then
also
that
Niche
is
reinforced
by
other
things.
So
it
could
be
like
you
know
what
the
cells
you
know,
how
do
you
get?
How
do
you
establish
a
niche
in
a
in
a
in
a
developing
organ,
and
so
people
have
been
interested
in
this
idea
of
stem
cell
Niche?
C
You
know
it's
possible
to
look
at
an
organoids,
it's
possible
to
look
at
in
culture,
but
it's
really
hard
to
kind
of
replicate.
This
paper
talks
about
cellular
shape
as
reinforcing
Niche,
so
the
abstract
reads
in
each
derived:
factors
regulate
stem
cell
tissue,
so
we
talked
about
what
niches
are
and
Niche
derived.
Factors
are
things
that
the
fact
chemical
factors
that
exist
in
that
Niche
and
so
they
regulate
tissue
stem
cells,
so
they're
stem
cells.
C
You
find
precursor
cells
in
different
organs
in
different
tissues,
and
then
these
factors
are
going
to
play
a
role
in
making
in
enforcing
that
theme.
But
apart
from
the
McKenna
sensory
Pathways
and
we've
talked
about
those
in
terms
of
the
gonad
and
in
terms
of
multi-sensory
integration,
the
effect
of
Niche
geometry
is
not
well
understood.
So
what
they're
interested
here
is
a
niche
geometry
or
the
shape
of
the
niche
and
its
geometric
properties.
C
We
use
organoids
in
bioengineer
tissue
culture
platforms
that
demonstrate
the
conical
shape
of
lgr5
plus
small
intestinal
stem
cells.
So
this
is
a
type
of
small
intestinal
stem
cell
lgr5
is
just
positive
for
a
certain
marker
that
defines
that
cell
type
they
have
a
conical
shape
so
they're
using
organoids
and
bioengineered
tissue
culture,
so
they're
using
what
I
just
mentioned.
So
those
are
the
tools
that
we're
using
we're
not
doing
it
in
Vivo,
and
this
facilitates
this.
C
The
conical
shape
facilitates
their
self-renewal
and
function,
inhibition
of
non-muscle,
myosin,
II,
driven
apical
constriction,
which
is
a
form
of
pattern.
Formation
and
physical
constraint,
altered
I,
see
a
shape
and
reduce
Niche
curvature
and
stem
cell
capacity.
So
there's
a
non-muscle
myosin
driven
apical
constriction.
This
is
where
there's
a
construction
in
in
the
morphogenesis
of
this
Niche.
This
is
ultra
or
of
the
tissue.
This
is
altering
the
shape
of
the
niche
and
reduce
the
curvature
and
stem
cell
capacity
of
that
Niche.
C
So
we
have
some
natural
morphogenetic
process,
that's
altering
the
shape
of
the
niche
Niche.
Curvature
has
decreased
in
aged
mice,
so
we're
looking
at
mice
we're
looking
at
aging.
So
we
see
that
there's
a
decrease
in
this
Niche
curvature,
suggesting
that
sub-optimal
interactions
between
old
iscs
or
intestinal
stem
cells
and
their
Niche
developed
with
age.
We
show
that
activation
of
an
miic,
which
is
this
NM,
which
is
a
non-musal
myosin
and
iic,
a
phys
or
physical
restriction.
Young
topology
improves
in
Vivo
regeneration
by
old
epithelium.
C
We
propose
that
the
increase
in
lateral
surface
area
of
ises
and
these
bibrical
constriction
promotes
interactions
between
neighboring
cells
in
the
curve
topology
of
intestinal
niches
evolved
to
maximize
signaling
between
iscs
and
neighboring
cells.
C
So
this
curvature
actually
brings
cells
into
contact
chemically
in
in
signaling
wise,
and
so
it
actually
enables
regeneration
and
other
functions
of
differentiation
to
occur.
So
this
is
really
interesting,
this
this
architecture
of
the
Niche
within
the
tissue.
So,
let's
see,
if
there
are
any
figures,
that's
probably
usually
a
good
place
to
go
to
really
understand
this,
so
this
is
a
composite
figure
with
a
we
have
Amino
stating
of
an
intestinal
Crypt.
So
this
is
the
intestinal
Crypt,
where
you
have
stem
cells
that
emerge
and
they
have
to
differentiate.
C
B
is
where
you
have
intestinal
organoids
and
now
they're
using
organoids
stained
with
Floyd
effect
and
and
he
could
hear
them
so
the
F
form
of
f
acting
is
on
the
top
e
kid
hearing
is
on
the
bottom,
and
these
are
the
things
that
are
going
to
be
important.
These
molecules
are
going
to
be
important
later,
they're
actually
just
ways
to
identify
the
cells,
and
you
know,
there's
State.
C
So
this
looks
at
the
surface.
Blood
of
the
organic
crypto
means
that's
the
inset,
so
the
inset
is
here.
This
is
the
organoid
surface
curvature.
So
this
is
looking
at
the
sort
of
the
topology
of
this
and
you
notice
that
it
curves
like
this.
You
have
these
buds
or
other
things
and
there's
a
lot
of
curvature
in
this
surface.
So
this
is
actually
something
that
you
know
and
you
can
see
that
there's
a
relationship
between
some
of
these
factors
here
that
are
stained
for
and
this
curvature.
C
So
you
can
see
the
heat
CAD
hearing
is
important
in
the
curve,
the
curved
parts
of
this
structure
and
affect
and
is
larger.
We
found
in
the
middle
of
the
structure,
so
you
can
see
that
it
actually
affects
the
distribution
of
these
factors.
C
In
C
we
have
quantification
of
iseta
and
pan
of
cell
morphology
and
organoids.
So
this
just
tells
us
like
the
cellular
dimension
in
terms
of
microns.
So
it's
a
measure
of
like
the
topology,
and
you
can
see
that
there's
a
difference
here
in
these
different
conditions.
A
C
E
is
where
you
have
M
my
H9
knockout
induced
two
days
after
passage,
and
so
then
they
have
some
of
these.
Some
of
these
strains
in
the
master
Edge
organoids.
So
you
can
see
here
that
you
have
e,
so
you
can
see.
Let
me
see
if
I
can
get
up
here.
Okay,
so
you
have
different
types
of
stains
here:
gfp
tomato
which
are
just
different
types
of
fluorescent
markers
and
they
show
these
different
conditions
of
their
vehicle.
This
is
where
it
says
the
vehicle.
C
C
So
this
gives
you
an
idea
of
what
this
looks
like.
Basically,
you
have
this
topology.
You
have
this
change
in
topology,
this
curvature
and
that's
sort
of
the
normal
conditioner
and
then
what
happens
in
aging
is
that
this
curvature
decreases,
and
so
you
get
less
of
this
sort
of
activity
you
you
know
and
it
it
sort
of
impacts
regeneration.
So
the
crypts
are
not
as
accessible
and
the
cells
aren't
getting
the
signals
they
need
those
are
disrupted,
and
so
you
don't
get
the
Regeneration.
C
C
So
one
of
the
things
that
they
do
is
they
they
make
the
statement.
Prevention
of
apical
constriction,
Alters
ISE
shape
and
reduces
capacity
to
regenerate
so
they're.
Looking
at
whether
iscs
require
tissue
with
topology
for
their
function,
they
targeted
critical
formation
and
organoids
as
a
conditional
knockout
of
myh9,
one
of
the
two
epithelial
isoforms
of
nm2,
and
so
this
is
a
removal
of
this
from
the
epithelial
enlarge
the
size
of
form,
encrypts
demonstrating
a
loss
of
apical
constriction
and
reduce
their
number
suggesting
attenuated
ISE
functioning.
C
C
Chosen
concentration
of
nm2
Inhibitors,
effectively
prevented
formation
and
organoids
that
affecting
cell
proliferation
Mark
by
the
time
Corporation
of
this
Factor
here,
similar
to
the
NM
to
a
knockout,
we
observed
increased
width
and
reduced
number
of
Crypt
domains
indicating
the
nm2
activity,
not
actomyosin,
structure,
maintains
Crypt
shape
by
apical.
Constriction
is
corroborate's
previous
reports.
C
So
this
is
a
interesting
stuff
here,
and
so
we
can
actually
mimic
the
native
Niche
curvature.
So
in
organoids
we
don't
have
the
full
organ.
We
don't
have
the
in
Vivo
model,
but
we
do
have
this.
You
know
organoid,
that's
sort
of
approximating
what's
going
on
in
the
biology,
but
so
if
we
mimic
the
native
Niche
curvature,
we
can
actually
maintain
the
ISC
function.
C
We
can
see
this
in
the
organoid,
because
we
can
actually
bioengineer
a
scaffold
that
will
allow
us
not
only
to
mimic
that
curvature
but
see
what
happens
when
the
curvature
is
not
there
or
modified
in
different
ways,
and
so
we
try
to
rule
out
different
types
of
things:
Yap
activity
and
other
types
of
things,
so
we
can
focus
on
these
changes
in
this
change
in
shape.
So
this
shows
you
a
little
bit
of
what
they're
doing
here,
they're
building
these
or
they're
constructing
these
organoids
on
a
a
scaffold.
C
C
That
then
changes
their
development,
and
you
end
up
with
this
structure
that,
if
you
change
the
shape
one
way,
you
can
improve
the
ability
for
cells
to
incorporate
into
this
organ
formation,
and
if
you
disrupt
the
shape,
if
you
disrupt
the
topology,
you
can
have
them
go
the
other
way.
So
this
is.
This
is
basically
showing
how
this
works
in
an
organoid
model,
so
they're
seeding
this
and
they're
putting
in
you
know,
they're
putting
in
their
Source
materials,
they're
growing
them
up
in
these
scaffolds
and
then
they're
testing
their
hypotheses.
C
High
surface
the
volume
ratio
improved
signal,
reception
and
iscs,
and
so
this
is
something
that
you
see
actually
in
the
human
brain
with
a
lot
of
the
gyration
is
on
the
surface
of
the
brain.
So
we
have
these
gyroide
that
exist
on
the
surface
of
the
human
brain
and
mammalian
brains
in
general,
if
they
exhibit
this
sort
of
gerification
and
one
of
the
hypotheses
there
is
that
this
you
can
take
a
sheet
and
Fold
It
Up
and
things
come
into
close
contact
with
one
another.
C
What
they
find
here
is
a
very
similar
idea
that
if
you
take
a
tissue
and
instead
of
having
it
as
a
flat
sheet
fold
it
up
into
these
folds
and
this
sort
of
rigid
or
rubber
topology,
you
can
actually
have
a
high
surface
to
volume
ratio,
and
you
can
also
improve
signal
reception
in
these
chemical
niches,
and
this
improves
these
skirts
of
this
sort
of
regenerative
capacity
or
this
capacity
to
become
a
healthy
tissue.
C
So
it's
very
important
in
terms
of
keep
maintaining
the
health
of
the
tissue,
and
so
it's
it's
an
interesting
topic
that
you
know.
If
people
are
interested
in
covering
more,
we
can
talk
about
it
more.
My
other
group
we've
been
doing
this
stuff
with
what
we
call
metabrade
models
and
changing
the
topology
of
those
models,
the
model
things
that
are
not
necessarily
brains.
So
there
are
these
seminal
tissues
like
the
gut
or
other
areas,
and
this
is
exactly
kind
of
what
they're
talking
about
here.
C
C
You
know
we're
not
showing
this
in
an
in
Vivo
model,
but
I
think
the
Oregon
model
does
enough
to
give
us
a
good
idea
of
how
this
works,
and
so
we
have
these
equations
for
looking
at
lateral,
surface
area
volume
and
some
of
these
other
things
and
I
think
that
would
be
interesting
from
a
cell
modeling
perspective
to
see
if
we
could
model
these
types
of
you
know
curved
niches
and
see
what
they
look
like
and
you
know
maybe
play
around
with
them
somewhat
think
I
hope
you
learned
something.