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Essentials of Embryology > L7- Limb Development > Flashcards

L7- Limb Development Flashcards

1
Q

What are the 3 sections in the limb?

A
  1. Stylopod
  2. Zeugopod
  3. Autopod
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2
Q

What is the stylopod in the forelimb?

A

Humerus

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3
Q

What is the stylopod in the hindlimb?

A

Femur

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4
Q

What are the zeuogpod components in the forelimb?

A

Radius and ulna

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5
Q

What are the zeugopod components in the hindlimb?

A

Tibia and Fibula

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6
Q

What is the autopod in the forelimb?

A

Manus (wrist, palm and fingers)

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7
Q

What is the autopod in the hindlimb?

A

Pes (ankle, sole, toes)

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8
Q

What are the 5 key events in limb development?

A
  1. Initiation
  2. Outgrowth
  3. Patterning
  4. Morphogenesis
  5. Differentiation
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9
Q

Where are the cells that form the limb buds from?

A

They are recruited from the flank lateral plate mesoderm (found next to paraxial mesoderm with intermediate mesoderm between the two)

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10
Q

How is the development of the limb initiated?

A

Axial cue given from somite and/or intermediate mesoderm

Lateral plate mesoderm produces FGF10 and ectoderm produces FGF8 which are signalling molecules promoting outgrowth.

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11
Q

What are the 3 signalling centres patterning the 3 primary axes of the limb?

A

Apical ectodermal ridge (AER)= proximal-distal

Zone of polarising activity (ZPA)= anterior-posterior

Dorsal ectoderm= dorsal-ventral

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12
Q

How does the AER cause proximal-distal limb growth?

A

Fibroblast growth factors (FGF’s)

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13
Q

What is the evidence for FGF’s playing a role in proximal-distal limb growth?

A

FGF8 expressed in AER

Exogenously supplied FGF can rescue the defects caused by AER removal so FGF protein is a substitute for missing AER. (in chick)

FGF8/FGF4 double knockout mouse (genetic equiv to removal of AER) has disrupted limb outgrowth (but distal structures do form) so it shows FGF genes are needed for outgrowth.

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14
Q

What is the evidence for ZPA patterning the antero-posterior axis?

A

Experiment where extra ZPA was added to the limb bud resulted in extra digits forming as mirror images to another.

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15
Q

How does patterning by ZPA work?

A

Via the morphogen model where cell identity is determined by the gradient of the signalling molecule

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16
Q

What signalling molecule is released by the ZPA?

A

Sonic hedgehog (Shh) which causes ZPA like duplications in limbs if a bead of it is inserted into the limb bud.

It can act as a replacement for the ZPA.

Shh mutants show limb abnormalities in development.

17
Q

Why are interactions between the AER and ZPA important?

A

Disruption of one signalling centre will have consequences on another (deformities and polydactilies). There is a positive feedback loop between signals from AER and ZPA.

Signals from the AER (FGF) are required to maintain expression of Shh in ZPA.

If AER is cut out the ZPA collapses and Shh expression is lost. This is restored by insertion of FGF bead.

Ectopic Shh in the mesenchyme can induce the ectopic expression of FGF4 in the ectoderm.

18
Q

How does the dorsal-ventral patterning occur in the dorsal ectoderm?

A

Wnt-7A gene is found in the dorsal ectoderm which acts on

Lmx-1 which is a transcription factor expressed in the dorsal mesenchyme.

19
Q

What is the evidence f or Wnt7a and Lmx1 impacting dorsal-ventral patterning?

A

Misexpression of Wnt-7a in the ventral ectoderm leads to the ectopic induction of Lmx-1 in the ventral mesenchyme.

Genetic deletion of Lmx1b leads to loss of dorsal limb pattern in mouse.

20
Q

How does specification of hindlimbs and forelimbs occur?

A

Different genes are expressed in the forelimbs and hindlimbs.
Tbx5 is only in the forelimb.
Tbx4 and Pitx1 are only in the hindlimb.

21
Q

What is the evidence for Tbx4/5 and Pitx1 impacting limb specification?

A

Deletion of Tbx5 in the limb leads to the disruption of FGF signalling and a failure of forelimb initiation.

Insertion of Pitx1 gene to the forelimbs causes formation of two hindlimbs in mouse. `

22
Q

What is the Leibenberg Syndrome?

A

A condition that involves the misdevelopment of the arms- misregulation of Pitx1 (it is more active than normal).

Essentials of Embryology (10 decks)

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