Fig. 8. A proposed model for the molecular regulation of forebrain and FNP morphogenesis via epithelial-mesenchymal signaling interactions. (A) Spatial relations of tissues and expression domains in the rostral head are shown in a schematic sagittal section through a stage 11 embryo. FGF8 (pink) and SHH (yellow) are expressed in the neuroepithelium and FNP ectoderm. RARß and RXR
(blue) are detected in neural crest mesenchyme, and ALDH6 (green) is localized to ventral FNP ectoderm. The black dashed box indicates area drawn at higher magnification in B, where we propose the retinoid-mediated signaling events occur. (Step 1) Between stage 10 and stage 12, RA is synthesized in FNP ectoderm (based on expression of ALDH6), and signals through receptors in neural crest cells that populate the FNP (based on expression of RARß and RXR). Blocking this step between stage 10 and stage 12 either by citral inhibition of RA biosynthesis or by antagonizing the receptors, has similar downstream consequences. (Step 2) We hypothesize that a retinoid-dependent signal (currently unidentified) emanates from the neural crest mesenchyme and signals to the forebrain and FNP epithelia, maintaining expression of FGF8 and SHH. Alternatively, if retinoid receptors other than the ones we examined are present in the forebrain and FNP epithelia, then RA might also signal through them and maintain expression of FGF8 and SHH. (Step 3) The maintenance of FGF8 and SHH expression is required for survival of the neural crest mesenchyme. A loss of gene expression at this step leads to increased programmed cell death and decreased proliferation. (C) Similar patterns of gene expression are observed in embryos through stage 20. (Step 4) The continued expression of FGF8 and SHH enables the forebrain and FNP to undergo their patterned outgrowth.
