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#limb patterning

2 public questions tagged with this topic.

Tetrapod

Which molecule is involved in specifying digit identity in the autopod?

Digit identity within autopod depends on anterior-posterior gradient of Sonic hedgehog duration and concentration from ZPA. High prolonged SHH posteriorly prevents Gli3 repressor formation, induces Hand2, posterior HoxD13 targets specifying posterior digits 5 and 4 with ulnar characteristics. Low SHH anterior allows Gli3R to promote digit 1 thumb identity. Manipulating SHH bead exposure time converts anterior digits to posterior fate. Gli3 mutant mice show polydactyly with loss of identity gradient. Hence SHH provides instructional positional information defining digit morphological individuality through Gli transcription factor balance and BMP interactions.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: SHH gradient and digit identity, Gli3 regulation.

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Tetrapod

Which transcription factor is responsible for forelimb development in tetrapods?

Forelimb determination depends on T-box transcription factor TBX5 expressed in anterior lateral plate mesoderm rostral to hindlimb region. TBX5 directly activates Fgf10 transcription in forelimb field progenitors, triggering downstream Wnt3a and Fgf8 in ectoderm and establishing self-sustaining outgrowth loop. TBX5 loss-of-function mutations cause Holt-Oram syndrome featuring thumb and radial defects plus cardiac septal anomalies reflecting cardiac co-expression. Homozygous mouse knockout eliminates forelimb bud induction completely while hindlimbs remain normal, proving specific requirement. Ectopic TBX5 can induce additional wing-like bud in interlimb region experimentally.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: TBX5 in forelimb specification and Holt-Oram syndrome.

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