Random Flashcards
What controls post embryonic growth?
GHRF releases GH from the pituitary gland. GH inhibits GFRH and drives the production of IGF1 in bone, liver and locally. It also produces somatostatin which inhibits GH. In embryos, IGF drives growth not GH.
What is the purpose of hippo?
It is used for growth limitation like how rapamycin inhibits the TOR pathway. When inactive, YOKI/YAP/TAZ are in the nucleus promoting growth. When active they are removed from the nucleus. Inactivated by mechanical stress when cells are stretched out.
How is proliferation in the drosophila mesoderm controlled?
String is a phosphatase that activates cdks for patterning and proliferation. Expressed early in the mesoderm but they also express tribble which inactivates string to prevent proliferation while the mesoderm is undergoing invagination.
How does heart regeneration occur?
when a cut has been induced, the endocardium activates the epicardium which invades the area and expands rapidly to cover the wound. The newly formed muscle begins to express FGF which causes reformation of blood vessels. The epicardium then expresses neuregulin which stimulates cardiomyocyte cell division
What is the GF pathway?
It stimulates PI3 pathway which activates AKT which goes on the phosphorylate nuclear p21 to keep it out of the cytoplasm and cytoplasmic p27 to keep it from entering the nucleus
How can heart regeneration be induced post Nataly?
There is loss of Errb2 postnatally which is a co receptor for neuregulin. Can make a transgenic mouse with doxycycline inducible dominant active Errb2= smaller scarring
What is expressed in the proximal blastema?
RA which stimulates expression of Prod1, meis homobox genes and RarS2
What is the ligand to Prod1 which links nerve innervation to regeneration?
nAG
What signalling is required to form the head organiser?
Wnt signalling- Beta catenin in the nucleus. (inhibition of GSK3B)
How is molting stimulated?
When stretch receptors are activated, they activate ptt which stimulates molting
How is metamorphosis induced in frogs?
When they have an imbalance in prolactin and thyroxin. CHR is secreted by the hypothalamus which stimulates TSH by the pituitary gland which causes thyroxin production in the thyroid gland. Thyroxin positively feeds back on itself to insure that metamorphosis persists and is irreversible.
How does pVHL occur?
VHL is a tumour suppressor gene. HIF1a is hydroxylated at 2 prolines by proline hydroxylase which allows it to bind to VHL and is ubiquitinated and degraded by proteasome in normoxic conditions. When there is a mutation it can’t bind to VHL and binds to HIF1B and activates HIF target genes which promote angiogenesis, glycolysis and erythropoiesis which causes cancer
How does mutation of NF1 cause cancer?
Causes neurofibromatosis= small tumours around the PNS neurons. It codes for a Ras GAP which inactivates Ras- when in active, Ras is constitutively active
How does pRB act as a tumour suppressor gene?
Usually acts to inhibit E2F TF- when hyper phosphorylated it doesn’t bind to E2F and I can activate its target genes e.g. cyclin E to progress through the cell cycle- works through positive feedback to stimulate its own transcription. Also cyclin A inhibits it to prevent cyclin e production
What are examples of immunosuppressants and what are their mechanisms of action?
1) glucocorticoids bind to nuclear R to prevent cytokine production
2) ciclosporin= binds to inhibit calcinurin which is normally activated by Ca2+ which dephosphorylates NFkappaB which enters the nucleus to activate transcription of cytokines e.g. TNF alpha and IL-1
