L4: cell-cell interactions (TGF-β, FGF)

name the 2 major TGF-β families

TGF-β-like + BMP-like

name the molecules in the TGF-β-like family

TGF-βs, activins, nodal

name the molecules in the BMP-like family

BMPs, GDFs, AMH

how many dimeric ligands make up the TGF-β superfamily

>30

name the canonical signalling pathway of the TGF-β-like family

smad2/3

name the canonical signalling pathway of the BMP-like family

smad1/5/8

describe the basics of Smad signalling

binding of TGF-β ligand to 2 x type 2 Rs causes recruitment of 2 x type 1 Rs to the complex. once assembled, type 2 Rs phosphorylate type 1 Rs to activate them via multiple ser/thr residues

how is BMP signalling controlled

ligand traps bind to ligands to prevent them activating their receptors

what is Smad2/3 signalling required for

mesoderm formation

how many Nodal ligands do humans have

1

how many Nodal ligands do zebrafish have

2

name the zebrafish Nodal ligands

squint/cyclops

name the essential Nodal coreceptor

cripto

what phenotype is caused by cripto mutations

one eyed pinhead

what injection rescues oep mutants

type 1 R mRNA

how many members are in the FGF ligand family

22

how many FGF receptors are there

4

name the features of an FGF receptor

EC D1, D2, D3 ig-like domains, TM domain, IC kinase domains

acid box between D1 + D2, heparin binding site in D2

state the function of the acid box in an FGF receptor

represses signal until ligand binds

state the purpose of a HSPG (heparan sulfate proteoglycan)

EC modifiers of cell-cell signalling, required for paracrine FGF activation

describe the structure of a HSPG

protein core (TM, tethered, or secreted) + long chains of heparan sugars

state the affinity of paracrine FGFs to HSPGs and the consequence of this

high affinity - retained + act locally

state the affinity of endocrine FGFs to HSPGs and the consequence of this

low affinity - diffuse into bloodstream

what does FGF signalling trigger through the MAPK pathway

FOS activation + cell proliferation

what does FGF signalling trigger through the Akt pathway

activation of FOXO + cell survival

what does FGF signalling trigger through the Calcineurin pathway

activation of NFAT + cell motility

what human diseases are associated with FGFR muations

Apert syndrome, Pfeiffer syndrome, Achrondroplasia (dwarfism)