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lecture 16 Flashcards

1
Q

what are the dominos that fall

A

reactions of cells & proteins, interactions they make, signal transduction pathways they control

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2
Q

do all those dominoes fall at the same speed

A

no; not at the same speed/time, some processes are slowed down/sped up as necessary

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3
Q

what does speed of a response depend on

A

turnover of signaling molecules (like fast proteins are already made, slower proteins take time to be made etc.)

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4
Q

describe fast signals

A

use proteins already made just waiting for activation signaling to turn them on so they can bind & activate downstream signaling protein [seconds to minutes]

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5
Q

give an example of fast signals

A

rac1 triggering switch of GDP to GTP, activates Arp2/3, triggers formation of branched actin networks important for cell-cell junction formation & protrusion of leading edge of migrating cell

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6
Q

why is rac 1 fast

A

everything (rac1, actin, arp 2/3) is already expressed, just waiting for signal

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7
Q

what are slow signals

A

when the protein needs to be made / expression needs to be changed before the next domino can fall

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8
Q

give an example of slow signals

A

if you need to produce a new protein, signal needs to go into nucleus, need to have an activation of trans. regulator that increase/decreases expression of certain genes, produces messenger RNA processed in nucleus and then exported

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9
Q

basically what are slow signals

A

bunch of different steps, each one takes time

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10
Q

what does mesoderm form

A

somites

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11
Q

what are somites

A

paired blocks of mesoderm that form early in development, lie on either side

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12
Q

what do somites give rise to

A

vertebrae, muscles, connective tissue; depending on where they are in the embryo

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13
Q

how do somites occur

A

always in pairs, extend the length of the embryo

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14
Q

what do somites represent

A

differentiation (mesoderm differentiates into somites)

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15
Q

what does the fate of each somite pair depend on

A

where they are on embryo

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16
Q

what happens as the embryo elongates

A

mesoderm differentiates into somites

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17
Q

visually describe differentiation of mesoderm into somites

A

goes from uniform field of cells into morphologically distinct little squares

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18
Q

what part of embryo are somites formed

A

at head region

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19
Q

what happens as somites go from right to left

A

embryo itself is getting longer

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20
Q

basically describe what happens to somites as embryo elongates

A

head is stationary, tail is moving away from the head while somites are forming in same direction left to right

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21
Q

fundamental question

A

what controls the clocklike timing of somite creation, that leads to regularly spaced somites

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22
Q

what does mutation of notch lead to

A

delays formation of somites

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23
Q

what else does a mutation of notch lead to

A

morphology is a little screwed up (doesn’t have sharp boundaries)

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24
Q

what is the key component of this timing mechanism

A

notch

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25
what happens if notch is mutated
somites still form, just their size and position is disrupted
26
what specifically is Notch required for
timing of somite formation rather than formation itself [for coordinate segmentation of somites]
27
describe mechanism of Notch
lateral inhibition; protein X is delta, notch is receptor for delta
28
what is lateral inhibition for
way for a uniform field of cells to differentiate into 2 diff cell types
29
who is delta expressed by
expressed by one cell that acts on its neighbor trying to turn off delta
30
who expresses Notch
both cells express notch, it's in plasma membrane
31
where in cell is delta expressed
also plasma memmbrane
32
what kind of signaling is notch and delta binding
cell-cell contact dependent signaling
33
describe lateral inhibition w/r to delta & notch
botch cells express delta; when delta binds notch, it tries to block its expression of delta
34
does it lead to a stalemate forever or does someone win
one cell wins this competition --> one cell doesn't express delta while another cell expresses a lot of it
35
what does one cell expressing none while another cell expresses a lot of it mean
differentiation
36
describe the receptor notch
latent transcription regulatory protein
37
describe the binding of notch and delta
cell-cell dependent signaling; notch in one cell, delta in another
38
what happens after notch and delta bind
triggers proteolytic event, tail of Notch enters nucleus where it acts like a transcriptional regulator
39
is lateral inhibition in somite formation
no; different processes, but they both use Notch
40
what is Hes
one of the genes controlled by notch fragment in nucleus (when it acts as a transcriptional regulator)
41
what is integral component of developmental clock that controls the timing of somite formation
expression of Hes
42
what activates notch
morphogens FGF and Wnt
43
where is notch activated
FGF and Wnt, when expressed, activate Notch in mesoderm
44
what does notch do and where
in mesoderm, it controls the production of Hes
45
what does a notch gene-expression oscillator act as
acts as a clock to control vertebrate segmentation
46
what happens in somite formation
tail is moving back, farther away from the head
47
what is occurring as the tail moves back
proliferation AND growth (embryo gets bigger)
48
what happens as tail elongates
uniform mesoderm is condensing and forming paired blocks of somites
49
what do the wavy blue lines represent
oscillations of Hes protein within that tissue
50
what does the line signify
level of Hes protein is oscillating, going up and down within individiual cells
51
how long is a cycle of Hes protein
90 mins
52
what happens as you get closer to presomitic mesoderm differentiating in to somiets
oscillations begin to slow down
53
which is produced first mRNA or Hes
mRNA first, because its mRNA and then protein
54
what needs to happen if we increase Hes expression
Hes mRNA has to increase first
55
what is secreted by the cells in the tail
Wnt and FGF proteins
56
what do Wnt and FGF maintain
maintain the oscillation of a transcriptional regulator within the presomitic mesoderm
57
what is the oscillation of this regulator required for
to prevent presomitic mesoderm from forming somites
58
what happens as Wnt and FGF move farther away
oscillations begin to slow down and eventually arrest
59
where/when is oscillating transcriptional regulator arrested at
either high expression or low expression
60
what is Hes protein that's oscillating a product of
notch signaling
61
what activates notch signaling
Wnt and FGF
62
where do Wnt and FGF come from
mesodermic cells at very tip of the tail
63
describe [ ] of Wnt and FGF
highest next to cells producing it, decreases the farther you go away
64
what dictates the oscillations of Hes
[ ] of Wnt and FGF
65
is this [ ] gradient static?
no; tail is growing, so the gradient is continuously shifting to the right
66
how is the highest concentration of Wnt and FGF moving
moving to the right
67
describe the rate of concentration
the concentration decreases at a rate equal to the growth of its tail
68
what is directly linked to how fast the tail is growing
when [ ] of Wnt and FGF slows down and arrest, it correlates to how fast tail is growing
69
if tail grows faster
soites form faster
70
what happens as source of wnt and fgf move farther away
oscillations slow down and eventually arrest
71
where the somites are formed is determined by what
relative expression level of Hes within tissue
72
are oscillations rapid?
yeah, Hes goes up and then down every 90 mins
73
describe signaling stuff closer to somites
Wnt and FGF much less concentrated, so notch signaling is not as active
74
what happens when these oscillations stop
cells are locked in place at level of Hes protein that they were expressed
75
does it mean cells have uniform level of Hes when they are stopped
naur
76
what dictates boundaries of somites
peaks and troughs; one edge is determined by peak, other edge is determined by trough
77
how can the length of somites be controlled
by changing the frequency of oscillations
78
what is the Hes gene essentially
essential component of this developmental clock... it's essentially the developmental clock
79
what is Hes doing
controls its own expression thru delayed negative feedback
80
what does delayed negative feedback lead to
oscillation
81
what happens to Hes once produced in cytoplasm
Hes protein moves into nucleus to turn off its own transcription (oscillation peak)
82
what happens to existing Hes protein
will be degraded over time due to normal protein homeostasis mechanisms
83
what happens after that to Hes
Hes gene transcription begins again (oscillation trough)
84
describe the end of the tail
Wnt and FGF in abundance, notch signaling is going full guns
85
what is Hes
inhibitory protein
86
is there Hes expressed at the starting point
no
87
what happens after this
notch is active (due to Wnt and FGF in high concentration), proteolytically cleaved and enters nucleus
88
what does notch turn on
expression of Hes
89
what happens as Hes and mRNA rises
mRNA exported to cytoplasm to create Hes, Hes enters nucleus and tries to turn itself off
90
how does hes try to turn itself off
thru delayed negative feedback
91
mRNA and Hes levels drop until what
drop until there's not enough Hes around to turn itself off
92
what happens after levels drop
mRNA and Hes are produced again, exported back to nucleus, turns itself off, begins to decrease
93
what are oscillations
delayed negative feedback of Hes BY Hes
94
what happens as tail moves away
oscillations slow until they become arrested
95
what are regions w/ high expression remaining
defined as one end of somite
96
what are regions w/ low Hes expression
other side of somite
97
what kinda protein is Hes
transcriptional regulator
98
what happens at the start
no inhibitory protein (no Hes)
99
what happens after notch pathway is activated
fragment of Notch that acts as its own transcriptional regulator enters nucleus, binds to DNA, recruits RNA Pol to produce Hes mRNA
100
what happens after mRNA is translated into protein at cytoplasm
Hes protein shows up
101
what is job of Hes
to turn itself off
102
what happens once it's produced in cytoplasm
Hes will be imported into nucleus thru nuclear pore complexes
103
what happens after Hes is imported into nucleus
binds to its own regulatory sequence (upstream of Hes)
104
how does Hes turn itself off
by preventing RNA pol from acting wit the gene
105
what do Wnt and FGF trigger
Hes segmental clock to form regularly spaced somites
106
what does this whole system, oscillations depend on
delayed negative feedback

bio 211 (18 decks)

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