Growth control

jambomber's version from 2015-05-12 10:16

Section 1

Question Answer
From where do signals converge on YAP/TAZECM cell cell adhesion and AM cytoskeleton
How does the Hippo pathway feed into YAP/TAZMST1+2 and LAt1_2 (Hippo and Warts) inhibit YAP/TAZ by P and preventing its entry into the nucleus
What regulates the hippo pathway?Cell adhesions + AB polarity complexes Ie Scribble + Crumbs
How do we know cell shape determines cell fateSpread dots of microprinted EXM (fibronectin islands) to control extent of endothilial cell spreading. Not a consequence of different extents of cell ECM contact. MSCs osteoblast and adipocytes
How do we know ECM stiffness alters fate?Culture cells on squares of diff stiffness- intermediate gives neurones etc
What effect does YAP overexpression have?Drives cells into believing they are on a stiff matrix
How do we know AM feeds into YAP control?Inhibiting Rho GTPases and thier ass cytoskeletal elements converts cell to a state of low tensile stess favouring
Under what conditions is YAP/TAZ permitted to enter the nucleus?Stiff Matrix, Spread widely-ie low cell density
how does AM feed into YAP control Does not appear to be G/F actin balance since G actin overexpression has no effect.Disrupting integrins and FA components effect YAP/TAZ localisation. Associated AM structures could therefore play a role (Ie Stress Fibres)
Model for YAP cotnrolContractile F actin develops due to integrin activation. These structures maintain YAPTAZ in nuclues through unkown mech which inhibits LATS kinase. Could it be the a YAP inhibitory factor is sequestered in these structures- revelation of cryptic bs?
What does attenuating YAP activation do?Potentiates growth promotion functions in vivo
What effect does YAP overexpression have?Overcome cell contact inhibition
What possible morphogen growth models could there be?1) Dpp permissive for growth and growth in periphery controlled by alt factors 2) Dpp is instructive for growth. Cells measure an independant property of gradient - ie discrepancies b/w cell or Temporal increases of Dpp
How many cell division occur in the wing disk- what is odd about them?10x division all cells divide at the same rate and contribute equally to the tissue
how does scaling effect the Dpp level a cell experiecnes?Relative postion always recives the same relative concentration
How could dpp influecne growth?Growth morphogen, point source which stimulates growth in centre and mech stress in periphery stimulates
Who proposed the gradient slope model? What caveats are there to this model?Day and LAwrence 2000 Assumes a linear slope of gradinet- not the case and doesn't consider scaling of gradient with time
Who reconciled Growth- Morphogen models?Wartlick 2011 Cells divide when relative Dpp levels increase by 50%

Section 2

Question Answer
What levels is growth regulated atOrgan, organism and b/w neighbouirng cells
How is organism level controlled?Hormones ie IGF1 and GH from pituitary tumours- gigantism + acromegaly
How is level of skeletal muscle controlled systemicallySkeletal muscles produce myostation which induces p21 cycle arrest in proliferating myoblasts
How do imaginal disks demo intrinsic control of growth?1)Damage- pupation is delayed as one disk is repaired. Other disk remains at appropriate size 2) Transplanted disks grow to the appropriate size in adults 3) Gorwth even arrested in permissive environments ie Eye disks in in vivo culture
What is the evidecne for intrinsic conrtol i vertabrates?Heart transplants initially grow @ donor gorwth rate 2) mouse humeri and pjalengeal bones of rates grow to the correct size and shape in diff species hosts
Intrinisic control in salamandersAmbystoma grafts of eye disk to limb buds- donor size. Transplantation of eye disks from small eyed to large eyed host retains normal size (PImctatum to tirgunium)
What is intersting about contorl of organ size?Independant of cell number- Compartment size constant when cell size manipulated via cell cycle ie newt cells adjust accoding to ploidy and rapdily dividing Drosophila cells form same sized region
Where is an example of mammalian independance of cell numbertetrapoid mouse embryos are 85% of the size of a normal mouse with 40% of the cells