L12: Branching Morphogenesis 1 Flashcards

1
Q

Why is branching effective?

A
  • Increase surface area for metabolic exchange while minimizing volume
  • Enable targeted delivery of nutrients while maximizing cell to cell contact
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2
Q

What are three main types of branching with examples?

A
  1. Single cell extension. (neurons)
  2. Collective cell migration (trachea)
  3. Non migratory mechanisms
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3
Q

What molecules acts as the internal guiding cue for filopodia retraction/extension?

A

++ pMLC leads to retraction through severing f-acting.

– pMLC and anchoring leads to extension

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4
Q

What are some positive external cues for neural path navigation?

A
  • Nerve growth factor
  • Brain derived growth factor
  • Netrin
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5
Q

What are some negative external cues for neural path navigation?

A
  • ephrin

- slit

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6
Q

NGF or BDGF pathway

A
> Receptor Tyrosine kinase
> PI3K
> PIP3
> GEFs
> activate Rac
> actin poly
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7
Q

Netrin Pathway

A

> activate FAK/src
activate Rac/Cdc42
acting poly

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8
Q

Which molecule does slit activate for actin depoly?

A

cofilin

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9
Q

Three reasons why drosophila trachea system is studied?

A
  • very simple model (~50genes, ~1600 cells)
  • Well documented
  • fluorescence microscopy
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10
Q

What are 3 stages of Tracheal development?

A
  1. cell commitment
  2. tracheal pit formation
  3. primary branching
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11
Q

What is the earliest sign of cell commitment?

A

Expression of Trh

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12
Q

How many placeodes are formed and how are they distributed?

A

20 bilaterally

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13
Q

Which sort of cell movement occurs during tracheal put formation?

A

Invagination

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14
Q

During invagination in pit formation, cells on which side forms the pits?

A

dorsal

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15
Q

Trh pathway?

A
Trh 
> EGFr 
> Rho-GAP 
> Apical acto-myosin enrichment 
> cell constriction (trapezoid like look) 
> cell invagination
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16
Q

Which element in the Trh pathway is self inhibitory?

EGFr / Trh / Rho-GAP

A

EGFr

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17
Q

Do cells divide after invagination?

A

No

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18
Q

Name some receptor tyrosine kinases

A

FGFr

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19
Q

How many cells are usually in the primary branch?

A

4-20

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20
Q

What is the earliest sign of cell commitment?

A

Expression of Trh

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21
Q

How many placeodes are formed and how are they distributed?

A

20 bilaterally

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22
Q

Which sort of cell movement occurs during tracheal put formation?

A

Invagination

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23
Q

During invagination in pit formation, cells on which side forms the pits?

A

dorsal

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24
Q

Trh pathway?

A
Trh 
> EGFr 
> Rho-GAP 
> Apical acto-myosin enrichment 
> cell constriction (trapezoid like look) 
> cell invagination
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25
Q

Which element in the Trh pathway is self inhibitory?

EGFr / Trh / Rho-GAP

A

EGFr

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26
Q

Do cells divide after invagination?

A

No

27
Q

Name some receptor tyrosine kinases

A

FGFr

28
Q

How many cells are usually in the primary branch?

A

4-20

29
Q

How many stereotypical positions for cell migration is there in primary branches?

A

6

30
Q

FGFr adapter protein is called

A

Dof

31
Q

Which chemoattractants are the 6 primary branches moving towards?

A
  • FGF
  • WG
  • BMP
32
Q

[T/F] Suppression of FGF through only FGF mutation (bnl) causes issues in tracheal development.

A

False. Any mutations in FGF signalling (i.e. FGFr mutant btl) can cause issues.

33
Q

How many types of FGF in drosophila?

A

3

34
Q

How many types of FGF in humans?

A

22

35
Q

What are some cellular mechanism FGF is used for?

A
Branching
Patterning
Differentiation 
Cell proliferation 
Cell survival
36
Q

How many types of FGFr in drosophila?

A

2

37
Q

How many types of FGFr in humans?

A

4

38
Q

[T/F] FGF is a powerful chemoattractant that promotes cell extension to the direction of the FGF source.

A

True

39
Q

FGFr adapter protein is called

A

Dof

40
Q

Describe one pathway downstream to FGF

A

FGF > bind to FGFr > Dof (adapter) >
> Grb2/drk > Sos > phosphorylate Ras >
> src64 >
> Raf > MEK/Dsor > MAPK/erk > Pnt + Ap1

41
Q

What is one possible explanation of the FGF source locations being the same in every scenario.

A

Global segment patterning system

42
Q

[T/F] Activation of Raf is essential to FGF signalling pathway

A

True. Raf is the only protein that can activate MAPK and lead to transcription factor Pnt to be activated

43
Q

In a normal circumstance where placeodes are already formed, do the pit formation mechanism also follow? Why?

A

Yes it does. Trh which leads to placeodes, also activate btl, dof and rho

44
Q

Which 3 proteins are produced downstream of Trh>

A

btl, dof, rho

45
Q

What are the cells closest to FGF sources called?

A

tip cells

46
Q

How many tip cells follow FGF sources in primary branching?

A

2

47
Q

[T/F] FGF leads to lamillepodia formation in tip cells

A

False. Filopodia is formed

48
Q

Can filopodia formation be rescued with ectopic insertion of FGF?

A

Yes

49
Q

[T/F] There is a pulling behaviour by tip cells on cells in the back.

A

True

50
Q

What is one possible explanation of the FGF source locations being the same in every scenario.

A

Global segment patterning system

51
Q

How many secondary branches come from 1 placeode?

A

~24

52
Q

[T/F] All secondary branches merge with neighbouring secondary branches.

A

No. Only fusion cells are responsible for that. T

53
Q

How many fusion cells per placeode?

A

~5

54
Q

When in AEL do secondary branches start growing?

A

~10

55
Q

When in AEL do fushion cells start growing?

A

~10-12

56
Q

Describe how FGF expression is different in 2* branches compared to 1* branches.

A

In 2* branches, FGF sources are dynamic. The FGF concentrations come in multiple concentrations at different time intervals. The sources also move slightly farther in each interval. The second wave causes 2* branches.

57
Q

3* branches are formed in response to what?

A

hypoxia

58
Q

Sprouty inhibits what?

A

Tyrosine Receptor Kinase signalling

59
Q

What problems are seen in the absence of sprouty?

A

Excessive 2* branches in wrong time and place

60
Q

[T/F] Branching is followed by physical and adhesion molecules, other than just chemoattractants

A

True.

61
Q

Draw the reiterated pathways for 1/2/3* branching.

A
62
Q

Which transcription factor is needed for 2* branching

A

pnt

63
Q

Which transcription factor is needed for 2* branching

A

blistered