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Cell biology > Lecture 18 > Flashcards

Lecture 18 Flashcards

1
Q

What is TGF-beta

A

Transforming growth factor-beta

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2
Q

Other than TFG-B what else comes under this family?

A

Bone morphogenetic proteins (BMPs)

Activin

Nodal

Decapentaplegic (Dpp)

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3
Q

Function of TGF-Beta proteins

A
  • Cell division stimulation and inhibition
  • Cell adhesion and extracellular matrix
  • Induction and cell specification in development
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4
Q

Explain TGF-beta family processing

A
  • Secreted as inactive precursors
  • leader region required for secretion into ER
  • Pro-domain cleaved in ER/Golgi secretory pathway
  • Mature domain contains 110-140 amino acids
  • Dimerize to be active - homodimer or heterodimer
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5
Q

Type I beta receptor

A

55kD
Transmembrane
Serine/threonine kinase

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6
Q

Type II Beta receptor

A

85kD

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7
Q

Type III beta receptor

A

285kD
Proteoglycan

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8
Q

How are TGF-beta receptors identified?

A

Add radioactive TFG-beta to cell

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9
Q

Explain a simplified version of the TGF-beta signalling pathway

A
  1. TGF-beta dimer binds dimer of type II receptor
  2. Receptor tetramer formed (2 type II and 2 type I)
  3. Type II receptor phosphorylates cytoplasmic domain of type I receptor
  4. Kinase activity of type I activated
  5. R-Smad phosphorylated by type I recepotr
  6. Phosphorylated R-smad binds co-Smad
  7. R-Smad/Co-Smad dimer enters nucleus
  8. Smad dimer forms complex with DNA-binding protein
  9. Complex binds near target genes and activates transcription
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10
Q

Specificity of TGF-beta

A

Various type I/type II receptors

Various R and Co-Smads where combination determines promoter target

TGF-beta - Smad2 and Smad4 dimer
BMP2 - Smad1 and Smad4 dimer

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11
Q

What is the specificity of R-Smad determined by?

A

3 amino acids in type I receptor

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12
Q

What are TFG-Beta family members involved in?

A

A-P and C-V axis specification in vertebrates and invertebrates

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13
Q

Explain fertilization

A
  • Point of sperm entry determines ventral aspect in D-V axis specification
  • Sperm binding causes microtubule based rearrangements
  • Cytoplasm rotates towards entry point
  • Dorsal side develops Niewkoop centre
  • Cleavage divisions
  • Develops to blastula
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14
Q

Explain Xenopus gastrulation in A-P axis specification

A

Forms gut and primary germ layers

Blastula to Gastrula

Mesoderm forms from marginal zone - mostly overlying archenteron (anus and mouth)

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15
Q

What are neural crest cells?

A
  • Specialist migratory populations
  • Migrate on cranial, dorsolateral, and ventral pathways
  • highly migratory, invasive and proliferative
  • Include melanocytes and adrenal medulla forming cells
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16
Q

Explain mesoderm fate in D-V axis specification

A

D –> Notochord –> Somites –> Kidneys –> Blood –> V

17
Q

What do dorsal and ventral vegetal cells incude from animal cap cells?

A

Dorsal -> Muscle and notochord

Ventral -> Blood and associated tissue

18
Q

The organiser in bastulas

A

Cut blastula in half

Dorsalising signal required

Coculture with dorsal marginal zone contains organizer - lots of muscle

Coculture with dorsal marginal zone contains organizer

19
Q

What 3 signals specify mesoderm

A

Dorsal signal

Ventral signal

Dorsalising signal

20
Q

What form 3 signals of mesoderm

A

TGF-beta proteins antagonists and antagonists of antagonists

21
Q

List antagonists of TGF-beta proteins

A

Nodal related = primary signal from vegetal hemisphere -> indues mesoderm in marginal zone

High nodal-related - dorsal mesoderm/organiser

Low nodal-related - Ventral mesoderm

22
Q

What induces ventral mesoderm formation

A

BMP4

23
Q

What antagonises BMP4 and dorsalises mesoderm

A

Chordin

24
Q

What does xolloid do?

A

Metalloprotease - Cleaves chordin allowing BMP4 to act

25
Q

Explain mesoderm inducing signals

A
  1. BMP4 expressed in marginal zone - induces ventral mesoderm
  2. TGF-beta induce nodal related in vegetal hemisphere
  3. Beta-catenin boosts nordal-related in Nieuwkoop centre = DV gradient -> induces dorsal mesoderm and organiser by nodal-related
  4. Chordin antagonises BMP4 - dorsal mesoderm
  5. Xolloid cleaves chordin - allowing BMP4 - ventral mesoderm
26
Q

Gastrulation in Drosophila

A

Cell fate specified on DV axis on blastoderm

Gastrulation happens in the same way

Mesoderm folds inwards - most central part of embryo forms mesoderm

More ventrally cells form epidermis or nerves - then epidermis only

Amniserosa is extraembryonic membrane

DV axis defined by cell fate change

27
Q

How does Dpp specify dorsal cell fates

A
  • Dpp closely related to BMP4

When BMP4 specifies ventral fate, Dpp specifices dorsal fate

28
Q

How is D-V axis specification conserved

A

Sog (Short gastrulation) is homolog of chordin

Antagonises Dpp - prevents dorsaling of ventral tissue

Sog cleaved by Tolloid protease - allows Dpp dorsaling

Cell biology (22 decks)

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