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Question

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

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Explanation

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.

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