18. TGF-ß family in development Flashcards
name 3 members of the TGF-ß family
nodal
bone morphogenetic proteins (BMPs)
decapentaplegic (Dpp)
name 3 functions of the TGF-ß family
stimulate and inhibit cell division
alter growth factor synthesis
induction
what must occur to activate members of the TGF-ß family
dimerisation
describe the structure of TGF-ß members
2 TGF-ß members held together by cysteine bonds
tight, compact structure = stabilises it preventing degradation
must be dimerised to become active
what are type 1 TGF-ß receptors
transmembrane receptors
e.g. serine kinases
what are type 3 TGF-ß receptors
proteoglycan, found only in a subset of cells
which is the largest TGF-ß receptor
type 3 = 285kD
describe the TGF-ß signalling pathway
- type I and type II dimer binds to form a tetramer
- type II receptor phosphorylates cytoplasmic domain of type 1 receptor
- kinase activated via phosphorylation
- R-smad phosphorylated by receptor
- phosphorylated R-smad binds to co-smad
- r-smad/co-smad complex enters the nucleus
- binds to DNA binding protein = activating transcription
what are TGF-ß family members involved in
axis specification
give 2 types of axis in animals
anterior - posterior
dorsal - ventral
what determines the torso-ventral axis in amphibian development
sperm entry
what happens when a sperm binds
microtubules contract across the cytoplasm, making the cytoplasm rotate and a signalling centre develops on the dorsal side
what is the name of the signalling centre that develops on the dorsal side
the nieuwkoop centre
describe the process of neurulation
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
what germ layer derives the neural tube
ectoderm
what are somites
bilaterally paired blocks of mesoderm that form along the dorso-ventral axis
what do somites form
dermis, skeletal muscle, cartilage, tendons and vertebrate
what is mesoderm fate dependent on
dorso-ventral axis positioning
what does the most dorsal aspect of mesoderm develop into
notochord
what does the most ventral aspect of mesoderm develop into
blood
signals from what two types of cells induces mesoderm formation
cap cells and vegetal cells
what induces the organiser
the nieuwkoop region
what happens if the organiser is transplanted
results in a new axis forming
what are the three signals that specify mesoderm
- ventral signal
- signal from nieuwkook centre (dorsal signal)
- organiser producing dorsalising signal
what is another name for the organiser
the spemann organiser
give an example of tgfß family proteins
nodal related
what hemisphere is nodal-related from
the vegetal hemisphere
what do high-levels of nodal-related induce
dorsal mesoderm formation
organiser
what do low-levels of nodal-related induce
ventral mesoderm formation
BMP4 also belongs to the TGFß family, what does this induce
ventral mesoderm formation
IT IS THE VENTRAL SIGNAL
what is chordin an antagonist of
BMP4
what is the function of chordin?
dorsalises mesoderm -
by preventing the ventralising activity of BMP4
allowing dorsal mesoderm to form
what is the function of xolloid
a metalloprotease that breaks down chrodin IN VENTRAL CELLS allowing BMP4 to act
what is the difference between BMP4 and Dpp
BMP4 specifies ventral fate
Dpp specifies dorsal fate
what happens if you inject Dpp mRNA into a mutant lacking Dpp
acts as a morphogen and can generate dorsal features:
- amnioserosa, dorsal epidermis
name a homolog of chordin
short gastrulation (Sog)
what is the role of Sog
antagonises Dpp preventing it from dorsalising ventral tissue
what cleaves Sog
tolloid protease
