Donovan 3 Flashcards
What is the important role of Igf2?
Binds to Igf2 receptor (sink) and Igf1 receptor (uses this to signal growth)
- Igf2 receptor prevents binding to Igf1 thereby REDUCING growth
- was a correction from lec 2*
What is the fate of germ cells?
Sperm and Ovum
What are common developmental mechanisms?
1) Cell-cell interactions Cell adhesion Junction formation Signaling centers 2) Morphogenetic movements Migration of individual cells Coordinated movement of groups of cells 3) Cell growth and proliferation Increase in size, number of cells 4) Cell death Programmed cell death 5) Differential gene expression Differentiation
Where do germ cells first arise? What molecule signals it?
At the end of the epiblast that will become caudal end of embryo
-Appearance of PGDs is brought by signaling of bone morphogenetic family of growth factors (BMPs) which are part of transforming growth factor-beta (TGFb)
What is the pathway of TGF-b?
Uses Smad pathway
1) TGFb (ligand) causes receptors to dimerize (heterodimer) which autophosphorylate each other 2) this dimer phosphorylates Smad, activating it so that i can enter the nucleus and activate target genes
**there are multiple Smads and BMPs
How does BMP4 release to induce formation of PGCs?
- acts in paracrine fashion
- release of BMP4 acts on local cells that have the receptor for it
- those differentiate into PGCs
- cells too far away don’t have enough concentration and thus don’t follow the same pathway
What is needed for germ cell specification?
1) active gene transcription: BMP signaling in PGCs
2) Active gene silencing or repression: Blimp suppresses somatic genes
What is BLIMP1’s function?
- B lymphocyte maturation (B lymphocyte-induce maturation protein)
- BUT MORE IMPORTANTLY: blocks the somatic cell differentiation of PGCs
From the caudal end where do the germ cells go?
Morphogenetic movement from caudal epiblast to gut tube (movement happens as new lineages form and the cells are “pushed” into the gut)
From the gut where do the PGCs go?
They migrate out of the gut and into the hindgut mesentery (toward descending aorta) and towards the develop gonads.
PGCs are the “hotdog” in the “bun” (gonad)
How do the cells migrate to gonad?
- Active cell migration
- Cell substrate adhesion (used to follow correct path; imagine ice skates for land vs. ice)
- Chemotaxis
- Regulated apoptosis (use to destroy cells that migrate to wrong place)
What happens if a germ cell does not follow the right path?
If they don’t migrate to right place, they undergo programmed cell death (apoptosis)
What is the role of integrins?
Allows for cell adhesion to fibronectin and laminin. Also allow for actin polymerization (lamellipodia). Without it, PGC make it to gonad in highly reduced numbers
-act through a phosporylation cascade involving Src and FAK
What is the KIT signaling pathway?
KIT uses a tyrosine kinase to phosphorylate many different pathways.
-one of which is PI3K which in turn activates AKT. This is important in cell survival and proliferation and adhesion
What happens in mutation of C-Kit?
No germ cell signaling so we get severely reduced number of germ cells.
-low germ cells numbers can stimulate the tissue more and can lead to ovarian or testicular cancer