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Advanced developmental biology > L12 : Skeleton > Flashcards

L12 : Skeleton Flashcards

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1
Q

where does skeleton of the body axis originate?

A

sclerotome only

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2
Q

what tf contribute to sclerotome

A

pax 9 and pax1

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3
Q

where does the limb skel originate

A

lateral plate mesoderm

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4
Q

what are teh three origins of the overall skeleton

A

sclerotome
somite
lpm

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5
Q

how do the first skeletal strucutres form

A

through pre-cartilage condensation

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6
Q

what is important about ecm in the early skeletal mesenchym

A

contains lots of hyaluronan

a glycosaminoglycan which serves as a cell spacer

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7
Q

what are the mechanisms of pre cartilage condensation

A

change in ECM
expression of enz that removes hyaluronan
alternative splicing of fibronectin - exon EIIIA only
present in condensing state only
expr of N-CAM nd N-cadherin
occurence of gap junctions

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8
Q

how doe migrating precursor cell turn into skeltal tissue

A

pre cartilage condensation

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9
Q

how is the skeletal tissue subdivided into specific bones

A

Hox gene role in limb patterning

in joint - imbetween hox/signal pathways/ muscle contraction

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10
Q

what signalling pathways do joints require

A

Wnt/BMP/GDF5/Ihh/integrins

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11
Q

what instigates the chnage from joint progenitor cell to commited joint cell

A

muscle contraction

shown by KO

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12
Q

what is the process through which bones elongate in dev

A

endochonral ossification

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13
Q

what is endochondral ossification

A

cartilage tunring into bone

range of differentiation steps

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14
Q

how is cartilage made

A

cartilogeneiss

mesenchyme condensation

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15
Q

what are some of the transitions in differentiation steps

A

chondroblasts in resting zone
columanr chondrocytes (prolif)
pre-hypertrophic chondrocytes (transition state not prolif)
hypertrophic transition start secretig ECM and increase in vol therfore become mineralised and sttract blood vessels
chondrocyte prolif and matix secretion = bone growth

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16
Q

what is the role of osteoblasts

A

accompany vascular invasion
become bone collar
cell which secrete the substance of bone

17
Q

what happens at puberty

A

growth plate disappears (epiphyseal fusion)

18
Q

where is the proliferation capacity ?

A

in resting zone cells

if transplant show young have the incr growth

19
Q

what are some systemic factors involved in senescence

A

igf
thyroid (hypo = low growth)
estrogen (castration before pub incr bone growth)

20
Q

what are the three principles of signal for bone growth

A

ECM
TF
long range signals

21
Q

when are diff collagen expr

A

early chondroblast and columnar chondroblast - col2a1
pre-hyp chondrocyte - hypertrophic chondorcyte - col10a1
osteoblasts expr col1a1

22
Q

what the ptype of mut col2a1

A

kniest disease
and types of dysplasia
mut affect chondrocyte survival /decr bone growth

23
Q

what the ptype of mut col10a1

A

ko viable and normal
but dom mut have metaphyseal chondrodysplasia type schmid
autosomal dom mut collagen X - shortened stature /growth plates abn

24
Q

what is the role of SOX9

A

master reg of chondrogenesis
dbl mut - no expr of chondrocyte specific markers
req for all aspects of limb dev

25
Q

how does sox9 act col2a1

A

direct

and indirect sox5/6

26
Q

what the role of sox5/6

A

act col2a1

ko display severe generalised chondrodysplasia

27
Q

what is the role of BMP in chondroblasts

A

is a potent inducer of chondorgenic and osterogenic fates

support prolif of chondorcyte in growth cartilage induce expr ihh

28
Q

what is the role of Runx2

A

promotes chondrocyte differentiation
promotes eo
ko loss of bone size

29
Q

how is runx2 regulated

A 
act ihh promoter
inh by PTHrP
role in neg feedback
induces expr Vegf in hypertrophic chondrocyte
and induce expr of Vegf-r in bone collar
30
Q

what is the role of Vegf

A

vegf attract endo cells

- vascularisation

31
Q

what is the interlink between osteoblasts and vasculature

A

accompany endo cells and depend on Vegf signals

32
Q

what is the role of MMP-9

A

expr chondroclast - help degrade cartilage ECM

33
Q

what long range signals involved in bone growth

A

ihh-PTHrP loop

wnt

34
Q

describe the ihh-PTHrP loop

A

PTHrP = ligand expr at early chondroblast
rec expr in chondro and hypertrophic chond
(promote ch prolif and inh Runx2 at cert distance)

runx2 act ihh
fgf inh ihh
ihh upreg PTHrP
ihh  = ligand expr pre-hyper ch 
          rec expr chondroblasts/cytes/ osteoblasts

keeps disticnt signal areas

Advanced developmental biology (18 decks)

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