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lecture 16 Flashcards

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Biology 101 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
Q

what happens if notch is mutated

A

somites still form, just their size and position is disrupted

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26
Q

what specifically is Notch required for

A

timing of somite formation rather than formation itself [for coordinate segmentation of somites]

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27
Q

describe mechanism of Notch

A

lateral inhibition; protein X is delta, notch is receptor for delta

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28
Q

what is lateral inhibition for

A

way for a uniform field of cells to differentiate into 2 diff cell types

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29
Q

who is delta expressed by

A

expressed by one cell that acts on its neighbor trying to turn off delta

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30
Q

who expresses Notch

A

both cells express notch, it’s in plasma membrane

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31
Q

where in cell is delta expressed

A

also plasma memmbrane

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32
Q

what kind of signaling is notch and delta binding

A

cell-cell contact dependent signaling

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33
Q

describe lateral inhibition w/r to delta & notch

A

botch cells express delta; when delta binds notch, it tries to block its expression of delta

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34
Q

does it lead to a stalemate forever or does someone win

A

one cell wins this competition –> one cell doesn’t express delta while another cell expresses a lot of it

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35
Q

what does one cell expressing none while another cell expresses a lot of it mean

A

differentiation

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36
Q

describe the receptor notch

A

latent transcription regulatory protein

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37
Q

describe the binding of notch and delta

A

cell-cell dependent signaling; notch in one cell, delta in another

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38
Q

what happens after notch and delta bind

A

triggers proteolytic event, tail of Notch enters nucleus where it acts like a transcriptional regulator

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39
Q

is lateral inhibition in somite formation

A

no; different processes, but they both use Notch

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40
Q

what is Hes

A

one of the genes controlled by notch fragment in nucleus (when it acts as a transcriptional regulator)

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41
Q

what is integral component of developmental clock that controls the timing of somite formation

A

expression of Hes

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42
Q

what activates notch

A

morphogens FGF and Wnt

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43
Q

where is notch activated

A

FGF and Wnt, when expressed, activate Notch in mesoderm

44
Q

what does notch do and where

A

in mesoderm, it controls the production of Hes

45
Q

what does a notch gene-expression oscillator act as

A

acts as a clock to control vertebrate segmentation

46
Q

what happens in somite formation

A

tail is moving back, farther away from the head

47
Q

what is occurring as the tail moves back

A

proliferation AND growth (embryo gets bigger)

48
Q

what happens as tail elongates

A

uniform mesoderm is condensing and forming paired blocks of somites

49
Q

what do the wavy blue lines represent

A

oscillations of Hes protein within that tissue

50
Q

what does the line signify

A

level of Hes protein is oscillating, going up and down within individiual cells

51
Q

how long is a cycle of Hes protein

A

90 mins

52
Q

what happens as you get closer to presomitic mesoderm differentiating in to somiets

A

oscillations begin to slow down

53
Q

which is produced first mRNA or Hes

A

mRNA first, because its mRNA and then protein

54
Q

what needs to happen if we increase Hes expression

A

Hes mRNA has to increase first

55
Q

what is secreted by the cells in the tail

A

Wnt and FGF proteins

56
Q

what do Wnt and FGF maintain

A

maintain the oscillation of a transcriptional regulator within the presomitic mesoderm

57
Q

what is the oscillation of this regulator required for

A

to prevent presomitic mesoderm from forming somites

58
Q

what happens as Wnt and FGF move farther away

A

oscillations begin to slow down and eventually arrest

59
Q

where/when is oscillating transcriptional regulator arrested at

A

either high expression or low expression

60
Q

what is Hes protein that’s oscillating a product of

A

notch signaling

61
Q

what activates notch signaling

A

Wnt and FGF

62
Q

where do Wnt and FGF come from

A

mesodermic cells at very tip of the tail

63
Q

describe [ ] of Wnt and FGF

A

highest next to cells producing it, decreases the farther you go away

64
Q

what dictates the oscillations of Hes

A

[ ] of Wnt and FGF

65
Q

is this [ ] gradient static?

A

no; tail is growing, so the gradient is continuously shifting to the right

66
Q

how is the highest concentration of Wnt and FGF moving

A

moving to the right

67
Q

describe the rate of concentration

A

the concentration decreases at a rate equal to the growth of its tail

68
Q

what is directly linked to how fast the tail is growing

A

when [ ] of Wnt and FGF slows down and arrest, it correlates to how fast tail is growing

69
Q

if tail grows faster

A

soites form faster

70
Q

what happens as source of wnt and fgf move farther away

A

oscillations slow down and eventually arrest

71
Q

where the somites are formed is determined by what

A

relative expression level of Hes within tissue

72
Q

are oscillations rapid?

A

yeah, Hes goes up and then down every 90 mins

73
Q

describe signaling stuff closer to somites

A

Wnt and FGF much less concentrated, so notch signaling is not as active

74
Q

what happens when these oscillations stop

A

cells are locked in place at level of Hes protein that they were expressed

75
Q

does it mean cells have uniform level of Hes when they are stopped

A

naur

76
Q

what dictates boundaries of somites

A

peaks and troughs; one edge is determined by peak, other edge is determined by trough

77
Q

how can the length of somites be controlled

A

by changing the frequency of oscillations

78
Q

what is the Hes gene essentially

A

essential component of this developmental clock… it’s essentially the developmental clock

79
Q

what is Hes doing

A

controls its own expression thru delayed negative feedback

80
Q

what does delayed negative feedback lead to

A

oscillation

81
Q

what happens to Hes once produced in cytoplasm

A

Hes protein moves into nucleus to turn off its own transcription (oscillation peak)

82
Q

what happens to existing Hes protein

A

will be degraded over time due to normal protein homeostasis mechanisms

83
Q

what happens after that to Hes

A

Hes gene transcription begins again (oscillation trough)

84
Q

describe the end of the tail

A

Wnt and FGF in abundance, notch signaling is going full guns

85
Q

what is Hes

A

inhibitory protein

86
Q

is there Hes expressed at the starting point

A

no

87
Q

what happens after this

A

notch is active (due to Wnt and FGF in high concentration), proteolytically cleaved and enters nucleus

88
Q

what does notch turn on

A

expression of Hes

89
Q

what happens as Hes and mRNA rises

A

mRNA exported to cytoplasm to create Hes, Hes enters nucleus and tries to turn itself off

90
Q

how does hes try to turn itself off

A

thru delayed negative feedback

91
Q

mRNA and Hes levels drop until what

A

drop until there’s not enough Hes around to turn itself off

92
Q

what happens after levels drop

A

mRNA and Hes are produced again, exported back to nucleus, turns itself off, begins to decrease

93
Q

what are oscillations

A

delayed negative feedback of Hes BY Hes

94
Q

what happens as tail moves away

A

oscillations slow until they become arrested

95
Q

what are regions w/ high expression remaining

A

defined as one end of somite

96
Q

what are regions w/ low Hes expression

A

other side of somite

97
Q

what kinda protein is Hes

A

transcriptional regulator

98
Q

what happens at the start

A

no inhibitory protein (no Hes)

99
Q

what happens after notch pathway is activated

A

fragment of Notch that acts as its own transcriptional regulator enters nucleus, binds to DNA, recruits RNA Pol to produce Hes mRNA

100
Q

what happens after mRNA is translated into protein at cytoplasm

A

Hes protein shows up

101
Q

what is job of Hes

A

to turn itself off

102
Q

what happens once it’s produced in cytoplasm

A

Hes will be imported into nucleus thru nuclear pore complexes

103
Q

what happens after Hes is imported into nucleus

A

binds to its own regulatory sequence (upstream of Hes)

104
Q

how does Hes turn itself off

A

by preventing RNA pol from acting wit the gene

105
Q

what do Wnt and FGF trigger

A

Hes segmental clock to form regularly spaced somites

106
Q

what does this whole system, oscillations depend on

A

delayed negative feedback

bio 211 (18 decks)

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