size determination Flashcards by Jenny Moore

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

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characterisitcs of specialised cell and the number

have little proliferation

10^14

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what makes animlas bigger than others

have more cells

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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

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what is primordial dwardfism caused by

mutation in pericentrin
involved in mitotic spindle
absence results in disorganised mitotic spindles and misegregation of chromosomes

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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

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what is tissue homoestasis

the replensihing of tissues by regulated prolieration and differentiation of somatic cells
involves highly coordinated control

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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

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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

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what is a mitogen

singal that encourage mitosis

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what regulates entry inton cell growth and division cycle

mitogenic signalling through ERK a RTK

signals to leave quiescent state

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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

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what role of hippo pathwya

inv in growth and inh
inh cell prolif
exit from cell cycle or cell death

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phenotype of mouose mutants in Yab

overexpr Yab in liver = increase size

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what are the drosophila counterparts for hippo pathway

yki instead of yab

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how does hippo mediated regulated

by cell cell contact
adhesion
apical basal polarity

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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)