18. TGF-ß family in development Flashcards

1
Q

name 3 members of the TGF-ß family

A

nodal
bone morphogenetic proteins (BMPs)
decapentaplegic (Dpp)

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2
Q

name 3 functions of the TGF-ß family

A

stimulate and inhibit cell division

alter growth factor synthesis

induction

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3
Q

what must occur to activate members of the TGF-ß family

A

dimerisation

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4
Q

describe the structure of TGF-ß members

A

2 TGF-ß members held together by cysteine bonds

tight, compact structure = stabilises it preventing degradation

must be dimerised to become active

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5
Q

what are type 1 TGF-ß receptors

A

transmembrane receptors

e.g. serine kinases

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6
Q

what are type 3 TGF-ß receptors

A

proteoglycan, found only in a subset of cells

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7
Q

which is the largest TGF-ß receptor

A

type 3 = 285kD

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8
Q

describe the TGF-ß signalling pathway

A
  1. type I and type II dimer binds to form a tetramer
  2. type II receptor phosphorylates cytoplasmic domain of type 1 receptor
  3. kinase activated via phosphorylation
  4. R-smad phosphorylated by receptor
  5. phosphorylated R-smad binds to co-smad
  6. r-smad/co-smad complex enters the nucleus
  7. binds to DNA binding protein = activating transcription
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9
Q

what are TGF-ß family members involved in

A

axis specification

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10
Q

give 2 types of axis in animals

A

anterior - posterior

dorsal - ventral

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11
Q

what determines the torso-ventral axis in amphibian development

A

sperm entry

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12
Q

what happens when a sperm binds

A

microtubules contract across the cytoplasm, making the cytoplasm rotate and a signalling centre develops on the dorsal side

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13
Q

what is the name of the signalling centre that develops on the dorsal side

A

the nieuwkoop centre

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14
Q

describe the process of neurulation

A

most dorsal region of the embryo becomes the neural plate

neural folds develop and fuse to form the neural tube

the brain forms at the anterior of the tube and the rest forms the final cord

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15
Q

what germ layer derives the neural tube

A

ectoderm

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16
Q

what are somites

A

bilaterally paired blocks of mesoderm that form along the dorso-ventral axis

17
Q

what do somites form

A

dermis, skeletal muscle, cartilage, tendons and vertebrate

18
Q

what is mesoderm fate dependent on

A

dorso-ventral axis positioning

19
Q

what does the most dorsal aspect of mesoderm develop into

A

notochord

20
Q

what does the most ventral aspect of mesoderm develop into

A

blood

21
Q

signals from what two types of cells induces mesoderm formation

A

cap cells and vegetal cells

22
Q

what induces the organiser

A

the nieuwkoop region

23
Q

what happens if the organiser is transplanted

A

results in a new axis forming

24
Q

what are the three signals that specify mesoderm

A
  1. ventral signal
  2. signal from nieuwkook centre (dorsal signal)
  3. organiser producing dorsalising signal
25
Q

what is another name for the organiser

A

the spemann organiser

26
Q

give an example of tgfß family proteins

A

nodal related

27
Q

what hemisphere is nodal-related from

A

the vegetal hemisphere

28
Q

what do high-levels of nodal-related induce

A

dorsal mesoderm formation

organiser

29
Q

what do low-levels of nodal-related induce

A

ventral mesoderm formation

30
Q

BMP4 also belongs to the TGFß family, what does this induce

A

ventral mesoderm formation

IT IS THE VENTRAL SIGNAL

31
Q

what is chordin an antagonist of

A

BMP4

32
Q

what is the function of chordin?

A

dorsalises mesoderm -
by preventing the ventralising activity of BMP4

allowing dorsal mesoderm to form

33
Q

what is the function of xolloid

A

a metalloprotease that breaks down chrodin IN VENTRAL CELLS allowing BMP4 to act

34
Q

what is the difference between BMP4 and Dpp

A

BMP4 specifies ventral fate

Dpp specifies dorsal fate

35
Q

what happens if you inject Dpp mRNA into a mutant lacking Dpp

A

acts as a morphogen and can generate dorsal features:

- amnioserosa, dorsal epidermis

36
Q

name a homolog of chordin

A

short gastrulation (Sog)

37
Q

what is the role of Sog

A

antagonises Dpp preventing it from dorsalising ventral tissue

38
Q

what cleaves Sog

A

tolloid protease