size determination

Question 1

what are the two ways growth occurs and what does growth have to balance

Answer 1

adding on cell number
adding on cell mass
balances growth and proliferation

Question 2

characterisitcs of specialised cell and the number

Answer 2

have little proliferation

10^14

Question 3

what makes animlas bigger than others

Answer 3

have more cells

Question 4

what is the phenotype of a sufferer if primoridal dwarfism

Answer 4

proporitonate reduction in sixe
average height 100cm
brain comparable to 3 month old baby
normal intellgence

Question 5

what is primordial dwardfism caused by

Answer 5

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

Question 6

what are some examples of disorders of deregulated cell proliferation resulting in tumorigenesis

Answer 6

proteus syndrome (PTEN)
Neurofibromatosis
tuberous scerosis
all deficiencies of the pr
all pr inc in proliferation and growth

Question 7

what is tissue homoestasis

Answer 7

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

Question 8

describe the action of receptor tyrosine kinases

Answer 8

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

Question 9

what three oathways of Ras important in cell proliferation

Answer 9

inc pop2 - bad inh apop/mTor stim pr synth/GSR-3B stim cell prolif
cdc42 - filopodia
rac- lamellipodia

Question 10

what is a mitogen

Answer 10

singal that encourage mitosis

Question 11

what regulates entry inton cell growth and division cycle

Answer 11

mitogenic signalling through ERK a RTK

signals to leave quiescent state

Question 12

describe the hippo pathway mechanism

Answer 12

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

Question 13

what role of hippo pathwya

Answer 13

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

Question 14

phenotype of mouose mutants in Yab

Answer 14

overexpr Yab in liver = increase size

Question 15

what are the drosophila counterparts for hippo pathway

Answer 15

yki instead of yab

Question 16

how does hippo mediated regulated

Answer 16

by cell cell contact
adhesion
apical basal polarity

Question 17

discuss the experiment that show regulation of hippo pathway by cell cell contact

Answer 17

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

Question 18

what is autonous growth and what is regulated growth

Answer 18

autonomous=not inf by growth of rest of body

regualtive = by external signals

Question 19

what experiment showed limb growth as autnomous

Answer 19

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

Question 20

what does liver do after injury

Answer 20

adjust to match organism size

Question 21

descirbe the experiment to show what growht in liver and pancreas

Answer 21

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

Question 22

what are the results from the liver/pancreas progenitor pool experiment

Answer 22

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)

Question 23

what are the three aspects of limb growth

Answer 23

girth
length
proportionality

Question 24

when fully growth what causes chnage in size

Answer 24

altered cell size

eg amount of adipose cells (adipose hypertrophy)/ muscle hypertrophy

Question 25

what controls embronic limb growht

Answer 25

fgf8 from AER

Question 26

descirbe endochondral ossification

Answer 26

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

Question 27

role of runx2

Answer 27

controls cartilagenous ossifcation

Question 28

what controls post natal limb evelopment/growth

Answer 28

bone growth and is regulated independently of the trunk skeleton.

Question 29

what are epiphyseal discs-

Answer 29

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

Question 30

what stimulates proliferation in the epihphyseal discs

Answer 30

insulin like growth factors

released into plasma y liver in response to GnRH from pituitary

Question 31

what results if too much growth hormone released from the piuitary due to tumour

Answer 31

if before puberty - increased height

if after puberty - groth of extremitites

Question 32

what are polymorphisms in Gh axis thought to explain

Answer 32

breedds in dogs - stature diffenrences

in humans pygmy tribe

Question 33

what is achondroplasia

Answer 33

short limb dwarfim

impaired growth of long bones

Question 34

what is the mutation that causes achondroplasia

Answer 34

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

Question 35

how does mut in FGFR3 cause achondroplasia

Answer 35

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

Question 36

what does mouse phenotype show

Answer 36

shorter limb but also smaller skull

Question 37

what is th ewild type role of fgfr3

Answer 37

norm inact monomer
when ligand bind = act
upregs when act cell cycle inh p16/p18/p19
limits proliferation of chondorcytes

Question 38

what other fgf involved in limb growth

Answer 38

FGF18
FGFR1 (more proximal thean FGFR3
FGFR2 (moer proximal than FGFR1

Question 39

what insight does the mut in FGFR3 provide

Answer 39

in evo devo the ev of altered limb trunk proportionality

Question 40

what is the eg for within limb proptiionality

Answer 40

mice and bats

have altered length of skeletal elements on the proximal distal axis

Question 41

what in dev produces bat wings

Answer 41

late prenatal growth of digits

- prior to this look the same

Question 42

what is the role of BMp signalling in bat forelimbs

Answer 42

Bmp 2/4 is secreted by the peristeum selectively in bat forelimb digits
= proliferation also increased (shown by bmp as activation of smad TF)