Foregut endoderm is required at head process stages for anteriormost neural patterning in chick

Anterior definitive endoderm, the future pharynx and foregut lining, emerge s from the anterior primitive streak and Hensen's node as a cell monolayer that replaces hypoblast during chick gastrulation, At early head process st ages (4+ to 6; Hamburger and Hamilton) it lies beneath, lateral to and ahea d of the ingressed axial mesoderm, Removal of the monolayer beneath and ahe ad of the node at stage 4 is followed by normal development, the removed ce lls being replaced by further ingressing cells from the node. However, simi lar removal during stages 4+ and 5 results in a permanent window denuded of definitive endoderm, beneath prechordal mesoderm and a variable sector of anterior notochord, The foregut tunnel then fails to form, heart developmen t is confined to separated lateral regions, and the neural tube undergoes n o ventral flexures at the normal positions in brain structure. Reduction in forebrain pattern is evident by the 12-somite stage, with most neuraxes la cking telencephalon and eyes, while forebrain expressions of the transcript ion factor genes GANF and BF1, and of FGF8, are absent or severely reduced. When the foregut endoderm removal is delayed until stage 6, later forebrai n pattern appears once again complete, despite lack of foregut formation, o f ventral flexure and of heart migration. Important gene expressions within axial mesoderm (chordin, Shh and BMP7) appear unaffected in all embryos, i ncluding those due to be pattern-deleted, during the hours following the op eration when anterior brain pattern is believed to be determined. A specifi c system of neural anterior patterning signals, rather than an anterior sec tor of the initially neurally induced area, is lost following operation. He terotopic lower layer replacement operations strongly suggest that these pa tterning signals are positionally specific to anteriormost presumptive fore gut, The homeobox gene Hex and the chick Frizbee homologue Crescent are bot h expressed prominently within anterior definitive endoderm at the time whe n removal of this tissue results in forebrain defects, and the possible imp lications of this are discussed. The experiments also demonstrate how stomo deal ectoderm, the tissue that will, much later, form Rathke's pouch and th e anterior pituitary, is independently specified by anteriormost lower laye r signals at an early stage.