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#digit formation

3 public questions tagged with this topic.

Morphogen Induction-l

Which morphogen regulates digit formation in vertebrate limb development?

Vertebrate limb anterior-posterior patterning and digit identity depend on Sonic hedgehog secreted from zone of polarizing activity in posterior mesenchyme under Hand2 and Hoxd13 control. Shh gradient high posterior specifies digit 5, intermediate specifies digits 4 and 3, low specifies digit 2, absence leads to digit 1. Shh induces nested Bmp2 antagonism and Gli3 repressor gradient establishing digit primordia via Gremlin loop. Ectopic Shh bead anteriorly induces mirror duplication and polydactyly. Myosin provides contractile force for shape changes, not positional code. Therefore Shh is key digit patterning morphogen via concentration-dependent patterning.

Ref: Tickle and Towers, Limb Development, Chapter 4: Shh Regulates Digit Patterning.

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Limb Development -l

Which signaling molecule is secreted from ZPA and regulates digit identity?

Digit identity along anterior-posterior axis is specified by Sonic hedgehog secreted from zone of polarizing activity at posterior border. SHH forms diffusible gradient anteriorly interpreted by Gli3 processing: high SHH posteriorly blocks Gli3 cleavage into repressor, elevating Gli activator specifying digits 5 and 4, while anterior low SHH allows Gli3 repressor specifying digit 1. FGF8 drives distal proliferation, BMP4 mediates interdigital apoptosis, Wnt3a initiates ridge. SHH simultaneously sustains apical ridge via induction of Gremlin1 that antagonizes BMP, coupling patterning with outgrowth maintenance and survival.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: ZPA sonic hedgehog gradient and digit patterning.

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Limb Development -lll

Which experiment demonstrated the importance of BMP signaling in digit formation?

Requirement of BMP in digit patterning was revealed by manipulating BMP antagonists experimentally. Overexpressing Gremlin1 or Noggin throughout digit plate in chick via RCAS retrovirus blocked BMP2-4-7 signaling, preventing both apoptosis in interdigital regions and chondrogenic condensation of phalanges, resulting in webbed, fused and truncated digits with reduced phalanges and syndactyly. Conversely, ectopic BMP application induces apoptosis and digit loss. Wnt7a knockout ventralizes dorsal limb, ZPA graft duplicates AP pattern, early AER removal truncates PD axis. Hence Gremlin overexpression experiment proved BMP necessity for digit formation and separation.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: Gremlin and BMP in digit morphogenesis.

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