Limb Formation3 Flashcards

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1
Q

Role of FGFs in P/D outgrowth

A

FGF10 in the limb bud mesenchyme induces the ectoderm to form the apical ectodermal ridge at the D/V junction
- FGF8 / FGF4 in the AER are required for limb P/D outgrowth

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2
Q

Conditional KO

A

Providing a tissue specific source of cre
(Tissue specific promoter + specific enhancer) + CRE
- Removes only from cells of interest
- Added with CRISPR

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3
Q

Genetic Redundancy

A

One FGF can compensate for the loss of another

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4
Q

Ectrodactyly

A

The absence or malformation of one or more central digits due to failure to maintain medical apical ectodermal ridge signaling.

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5
Q

Essentials of the AER

A
  • Controls P/D outgrowth
  • FGF4/8
  • First morphological distinction of the limb but
  • Ectodermal
  • Maintains progress zone
    • promotes proliferation
    • maintains undifferentiated state
    • prevents cartilage forming
  • induced by FGF10 with Wnt3 through the underlying mesenchyme
  • Maintains expression of molecules in ZPA
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6
Q

Progress Zone

A

Region of undifferentiated mesenchyme located beneath the apical ectodermal ridge. Provides pool of progenitor cells that proliferate and progressively differentiate to form the different segments of the limb
- P/D specification correlates with the age of the PZ mesenchyme

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7
Q

HOX genes

A
  • set limb but positions
  • pattern the P/D axis
  • Set location of ZPA
  • Pattern A/P of digits
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8
Q

How various surgical manipulations/transplantation experiments with the AER, PZ, and ZPA have helped reveal their functions

A
  • Removing AER results in no limb outgrowth
  • Replacing the AER with beads soaked with FGFs (FGF8) can rescue limb outgrowth
  • Transplanting a limb but with PZ and AER to a naive site leads to a complete limb. Meaning that the PZ possess the positional information necessary for P/D specification
  • Transplanting PZ mesenchyme of different ages to the distal tip of the limb but results in limb segments corresponding to the age of the PZ
  • Transplanting ZPA to the anterior leads to mirrored duplication of digits
  • Implanting beads soaked in SHH mimics ZPA transplantation
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9
Q

Opposing Gradient/Two signal model for P/D outgrowth

A

Retinoic Acid and FGFs/Wnt create a P/D gradient. Influence the fate of PZ cells

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10
Q

Basic idea behind Reaction-Diffusion Mechanisms

A
  1. Activator: activates itself and inhibitor
  2. Inhibitor: inhibits the activator
  3. Diffusion rates: the activator diffuses more slowly than the inhibitor.
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11
Q

Zone of Polarizing Activity (ZPA)

A

Specifies A/P axis
- ZRS - activates SHH
- SHH - sufficient for posterior activity
- Digit 5 has longes time of expression

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12
Q

Hx mutation

A

SHH mis-expression in Posterior and Anterior

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13
Q

Polydactyly

A
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14
Q

Triphalangeal thumb syndrome

A
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15
Q

Important Roles for gene regulatory sequences in development

A
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16
Q

How limb growth shuts down through BMP inhibition of FGFs

A

As limb grows

17
Q

FGF8 and FGF4

A
18
Q

Retinoic Acid

A
19
Q

FGFs/Wnts

A
20
Q

Meis

A
21
Q

Hox genes

A
22
Q

Cyp26

A
23
Q

Shh

A
24
Q

BMPs

A
25
Q

Grem

A