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Flashcards in BG13 Deck (30)
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1
Q

Limb axis

A

AP
DV
PD

2
Q

limb zones

A

stylopod -> humerus and femur
Zeugopod: radius and ulna
autopid: hand

3
Q

limb first formation

A

when limbs first form they are a sack of ectoderm filled with undifferentiated mesoderm.

4
Q

human development

A

appear around day 26 after conception
day 50 fingers vsiible
day 56 fetus can touch nose

5
Q

what do limbs form from

A

4 limb frield

6
Q

what did limbs develop from in different vertebrates

A

different somite levels

7
Q

how are homologous limbs defined

A

by the same hox gene expression along the AP axis

8
Q

give two examples of hox gene specification in limb development

A
  1. chicks have more cervial neck vertebrate than humans but the boundary is encoded by the same combo of hox genes.
  2. in fish/amphibians/birds and mammals, the forelimb buds are found at the most anterior expression region of hoxc-6 the position of the first throacic vertebrate
9
Q

what does RA do in limbs

A

specified limb fields via hox activity - produced by the organiser

10
Q

RA exposure to amputated tadpole tail

A

if exposed to ra in the first days of regeneration, several legs formed from tail as tail stump. as ra acitvates hox genes to form limbs

11
Q

what does the signal for limb formation come from

A

the lateral plate mesoderm that will become the prospective limb messenchyme
- cells secrete fgf10 paracrine factor

12
Q

ectopic addition of fgf10

A

added ectopically beneath flank ectoderm, extra limbs emerge

13
Q

mutation in fgf3

A

causes achrondroplasia dwarfism

14
Q

what did john saunders note

A

limbs were covered in ridge of unusual ectoderm

  • cells tightly packaed and columnar rather than pancake shaped
  • called apical ectodermal ridge
15
Q

what did saunders hypothesize

A

that it had something to do with proximal distal outgrowth and patterning of the limb

16
Q

what were saunders experiments

A

surgically removed Aer
- removal stopped limb outgrowth,
- removal interupted patterning of the limb
removed in young limb bud nearly all structures were lost. older limb only distal structures were lost

17
Q

Meromelia

A

partial failure of PD growth in one or more limbs in humans

18
Q

causes of meromelia

A

suggests due to failure of aer
however interdependence of aer with other signalling systems in limb means interpretation of these syndromes is not straightfoward

19
Q

AER and FGF

A

aer secretes fgf
specially fgf8
* remove aer but add fgf8 ectopic bead = still get more or less properly developed limb.

20
Q

fgfs in humans

A

around 20 in humans and other mammals, many expressed in the limb, several in aer

21
Q

clock model who proposed

A

summerbell

* model to explain how aer works and makes limb

22
Q

limb bud elongation

A

limb bud elongates by proliferation of mesenchymal cells under aer (progress zone) which extend 200nm from aer.
fgfs from aer keep progress zone mesenchymal cells dividing

23
Q

clock model

A

longer cells remain in the progress zone the more distal they become
stem cells maintained in the progress zone of proliferation and cells behind them dont proloferate as much and become specialised proximally.

24
Q

problem with the clock model

A

removal of aer only causes a reduction in proliferation of progress zone
*basis of model

** cell death also increases which is unexpected, aer is doing more complicated things.

25
Q

basis for pre-specification model

A

lineage tracing shows that even in the earliest limb bud - before growth has started, the cells were commmitted to becoming different parts along the PD axis; stylo/zeugo/autopod.
suggests pre-dermtinated pattern

26
Q

pre-specification model

A

proposed there is an initial population of cells that are pre-specificed in the ectoderm and that the aer merely maintained and expanded these populations

27
Q

aer removal explained by pre-specification model

A

proliferation occurs in a particular order, proximal proliferate first, then more distal - so removing aer kills a constant depth of cells 200m at all times,

  • done early affects cells of all future parts of the limb
  • done late however only affects most distal (autopod structures)
28
Q

recombinant limb technology

A

2011
rLs are limb buds made by dissociating mesenchymal cells from a limb bud; re-aggregating them and putting them in a jacket of limb bud ectoderm
recombinant limb buds can then be grafted back onto a new chick where it will grow.

29
Q

counter gradient model basis

A

if stage hh18 cells are formed into a rL and grafted back, they can form a proper three part limb.
cultured with wnt3a (another aer sig) and fgf8 they become increasingly restricted to form only distal structures.
culture with ra too form the full limb

30
Q

counter gradient model

A

suggests there is no clock but that the pd fate of the mesenchymal cells depends on balance between exposure to RA vs exposure to wnt3a and fgf8

  • experiments also show some patterning occurs later in development, so morphogen gradients form an extra later of pd patterning which is thought to control progresszone