Practice question

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.