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#signaling loop

2 public questions tagged with this topic.

Limb Development -ll

Which signaling loop maintains limb bud outgrowth?

Proximal-distal elongation and maintenance persist through reciprocal signaling between distal mesenchyme and apical ectodermal ridge. FGF10 from distal mesenchyme induces and maintains FGF8 in AER via Wnt3a beta-catenin pathway, and FGF8 sustains FGF10 transcription and proliferation through Pea3 Ets factors and ERK activation. This mutually dependent FGF10-FGF8 loop is reinforced by Gremlin blocking BMP to prevent AER involution and SHH enhancing Gremlin. Disruption causes progressive truncation with proximal elements spared. Wnt7a-FGF10 does not maintain PD elongation, SHH-BMP loop governs AP timing, PITX1-Wnt3a is not a maintenance feedback pair.

Ref: NCBI Bookshelf, Developmental Biology: FGF10-FGF8 loop maintains limb outgrowth signaling.

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Limb Development -lll

Which signaling loop maintains limb bud outgrowth?

Proximal-distal outgrowth relies on positive feedback between mesenchymal FGF10 and ectodermal FGF8 forming self-sustaining loop. Mesenchymal FGF10 activates Wnt3a beta-catenin cascade in ectoderm to induce AER formation and FGF8 expression in ridge cells. FGF8 then signals back to mesenchyme through FGFR1-2 activating Pea3 and maintaining FGF10 transcription, Gremlin expression and progress zone proliferation. This FGF10-FGF8 loop keeps limb elongating while balancing RA proximally via Cyp26b1. Interruption leads to truncation. SHH-Gremlin loop modulates BMP but does not directly drive PD outgrowth, Wnt7a loops pattern DV.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: FGF10-FGF8 feedback sustaining outgrowth.

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