size determination Flashcards
what are the two ways growth occurs and what does growth have to balance
adding on cell number
adding on cell mass
balances growth and proliferation
characterisitcs of specialised cell and the number
have little proliferation
10^14
what makes animlas bigger than others
have more cells
what is the phenotype of a sufferer if primoridal dwarfism
proporitonate reduction in sixe
average height 100cm
brain comparable to 3 month old baby
normal intellgence
what is primordial dwardfism caused by
mutation in pericentrin
involved in mitotic spindle
absence results in disorganised mitotic spindles and misegregation of chromosomes
what are some examples of disorders of deregulated cell proliferation resulting in tumorigenesis
proteus syndrome (PTEN) Neurofibromatosis tuberous scerosis all deficiencies of the pr all pr inc in proliferation and growth
what is tissue homoestasis
the replensihing of tissues by regulated prolieration and differentiation of somatic cells
involves highly coordinated control
describe the action of receptor tyrosine kinases
are growth factors
largest family
eg) tyrosine kinase
ligand bind -to TM pr - dimerise -autophosphorylate
activates the enzyme sos in the cells.
Sos is a GEF of RAs, activates multiple Ras = amplify
Ras activates multiple downstream signal cascades = allow cells grow and divide
what three oathways of Ras important in cell proliferation
inc pop2 - bad inh apop/mTor stim pr synth/GSR-3B stim cell prolif
cdc42 - filopodia
rac- lamellipodia
what is a mitogen
singal that encourage mitosis
what regulates entry inton cell growth and division cycle
mitogenic signalling through ERK a RTK
signals to leave quiescent state
describe the hippo pathway mechanism
using human names
sav1 interacts with Mst1/2 (pro apoptotic kinases)
act Mst1/2 phosphy and act Lats1/2 which form complex with Mob1. this complex phosphy and inh Yab/Taz transcription coact
what role of hippo pathwya
inv in growth and inh
inh cell prolif
exit from cell cycle or cell death
phenotype of mouose mutants in Yab
overexpr Yab in liver = increase size
what are the drosophila counterparts for hippo pathway
yki instead of yab
how does hippo mediated regulated
by cell cell contact
adhesion
apical basal polarity
discuss the experiment that show regulation of hippo pathway by cell cell contact
in low density yap on in nuc = proliferation
high density yap off in uc = growth arrest
= shows sense envdensity of cells
if disrupt cell cell junction in epi nuc localisation of Yap/Taz shows imp for hippo
what is autonous growth and what is regulated growth
autonomous=not inf by growth of rest of body
regualtive = by external signals
what experiment showed limb growth as autnomous
salamander limb transplantation
two diff species diff size
transplanted limbs growth to size would have
not inf by growht of the rest of the body
knows what size it should be
what does liver do after injury
adjust to match organism size
descirbe the experiment to show what growht in liver and pancreas
disturb no of precursor cell number by integrating teracycline transactivator in a locus of the TF that defines the cell type
when this tf expr = TA also expr in these cell only
eg pancreas - pdx1 / liver-lap
then have embry which can alter the amount of the pancreas and liver cells by the dose of teracycline
then give preg mice TA = no cell death
untreated = decr in cell type
what are the results from the liver/pancreas progenitor pool experiment
pancreas- smaller pancreas / no catch up growth the remiander cells can grow and divide and differentiate but can talter the rate they do this
liver- liver shows catchup growth within 4 days (lose 2/3 of mass and within 4 days is restored)
what are the three aspects of limb growth
girth
length
proportionality
when fully growth what causes chnage in size
altered cell size
eg amount of adipose cells (adipose hypertrophy)/ muscle hypertrophy
what controls embronic limb growht
fgf8 from AER
descirbe endochondral ossification
bone development in which the cartilage template laid out first then pssified to form bone
mesenchymal condensation to form a cartilage model of the bone to be formed. Following chondrocyte hypertrophy and cartilage matrix mineralization, osteoclast activity and vascularization result in the formation of the primary, and then secondary ossification centers. In mature adult bones, the growth plate is fully resorbed, so that one marrow cavity extends the full length of the bone
role of runx2
controls cartilagenous ossifcation
what controls post natal limb evelopment/growth
bone growth and is regulated independently of the trunk skeleton.
what are epiphyseal discs-
where groth of limb is restircted to at the end of bone
ossification only occurs here at puberty then stops
= chondrocytes proliferate in the proliferating zoen then beocme hypertrophic and die = recapitualte endochondral ossification in development
what stimulates proliferation in the epihphyseal discs
insulin like growth factors
released into plasma y liver in response to GnRH from pituitary
what results if too much growth hormone released from the piuitary due to tumour
if before puberty - increased height
if after puberty - groth of extremitites
what are polymorphisms in Gh axis thought to explain
breedds in dogs - stature diffenrences
in humans pygmy tribe
what is achondroplasia
short limb dwarfim
impaired growth of long bones
what is the mutation that causes achondroplasia
norm by mut in FGFR3 g380r (GOF)
80-90% spontaneous the rest transmitted in dom
the mut results in constiutive active FGFR3 independet of ligand binding
how does mut in FGFR3 cause achondroplasia
norm expr in long bones undergoing endochondral ossification
is a negative regulator of bone growth
mut - always active results in quicker ossification
growth plates are larger and more active
= process over quicker results in shorter limbs
decrease in number of proliferating chondrocytes
what does mouse phenotype show
shorter limb but also smaller skull
what is th ewild type role of fgfr3
norm inact monomer
when ligand bind = act
upregs when act cell cycle inh p16/p18/p19
limits proliferation of chondorcytes
what other fgf involved in limb growth
FGF18
FGFR1 (more proximal thean FGFR3
FGFR2 (moer proximal than FGFR1
what insight does the mut in FGFR3 provide
in evo devo the ev of altered limb trunk proportionality
what is the eg for within limb proptiionality
mice and bats
have altered length of skeletal elements on the proximal distal axis
what in dev produces bat wings
late prenatal growth of digits
- prior to this look the same
what is the role of BMp signalling in bat forelimbs
Bmp 2/4 is secreted by the peristeum selectively in bat forelimb digits
= proliferation also increased (shown by bmp as activation of smad TF)
