Which molecule is primarily responsible for mesenchymal proliferation beneath AER?
Progress zone concept holds distal mesenchyme beneath AER remains proliferative and undifferentiated under continuous FGF influence. AER-derived FGF8 signals through FGFR1 FGFR2c activating ERK MAPK and PI3K AKT pathways, upregulating Cyclin D1 D2 and maintaining FGF10, Gremlin and Spry expression to prevent precocious exit. This prevents premature Meis-driven proximal differentiation and keeps cells cycling, expanding progenitor pool for distal elements. Genetic deletion reduces proliferation and causes early differentiation and truncation. Wnt3a induces AER, BMP2 promotes apoptosis, SHH patt
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: FGF8 maintains mesenchymal proliferation beneath AER.