Local retinoid signaling coordinates forebrain and facial morphogenesis by maintaining FGF8 and SHH.

摘要: Correlations between facial anomalies and brain defects are well characterized throughout the clinical literature, yet a developmental basis for this association has not been identified. We demonstrate that frontonasal process, which gives rise to mid- upper face, forebrain linked early in their morphogenesis by local retinoid signaling event maintains expression of key regulatory molecules. First, we show aldehyde dehydrogenase 6, synthesizes ligand, retinoic acid, is localized ventral epithelium presumptive process chick embryos. At least two receptors expressed adjacent populations mesenchyme. Second, using synthetic pan-specific antagonists, transiently inhibit ability bind acid rostral head generate embryos with hypoplastic forebrain, fused eyes, no process-derived structures such as beak. These due eliminating mesenchymal progenitors, neural crest cells still migrate into despite disruptions signaling. Rather, these malformations result from loss fibroblast growth factor 8 sonic hedgehog expression, leads increased programmed cell death decreased proliferation process. Most significantly, can rescue morphological re-introducing or proteins antagonist-treated propose source initiates cascade coordinates morphogenesis.