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#feedback loop

2 public questions tagged with this topic.

Limb Development -l

Which molecule maintains the positive feedback loop between AER and mesoderm?

Persistence of limb outgrowth requires reciprocal positive regulation between apical ectodermal ridge and distal mesenchyme. Ridge-derived FGF8 sustains FGF10 expression in progress zone mesenchyme, and mesenchymal FGF10 reciprocally maintains FGF8 expression in ridge, amplified by sonic hedgehog from ZPA inducing Gremlin1 which blocks BMP-mediated repression of FGFs. Wnt3a initiates ridge formation, BMP4 drives interdigital apoptosis, Sox9 initiates chondrogenesis. Disruption of FGF8-FGF10 interchange rapidly collapses feedback causing ridge regression and cessation of elongation, establishing FGF8 as maintenance core and survival factor.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: AER-FGF8 and mesenchymal FGF10 positive feedback maintenance loop.

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Tetrapod

Which molecule maintains the positive feedback loop between AER and ZPA?

Interaction between ZPA and AER is maintained by positive feedback loop involving FGF8, SHH, Gremlin1 and BMPs forming self-sustaining circuit. SHH from ZPA upregulates Gremlin1, which antagonizes BMP activity that would otherwise inhibit FGF10 and FGF8 expression in mesenchyme and ectoderm. This permits FGF8 persistence in AER. FGF8 signals via Etv4/5 transcription factors to sustain Shh transcription through long-range ZRS enhancer. FGF8 therefore closes loop, ensuring coordinated outgrowth and anterior-posterior patterning. Disrupting FGF8 or applying BMP beads extinguishes Shh prematurely terminating elongation.

Ref: NCBI Bookshelf, Developmental Biology, Chapter 19: AER-ZPA feedback via FGF8, SHH, Gremlin and BMP.

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