Multistep signaling and transcriptional requirements for pituitary organogenesis in vivo.

作者：M G Rosenfeld, Paola Briata, Jeremy S. Dasen, Anatoli S. Gleiberman, Chrissa Kioussi, Ching‐Yu Lin, Shawn M. O’Connell, Aimee K. Ryan, Daniel P. Szeto, Mathias Treier · 发表于：PubMed · 年份：2000 · 被引用次数：83 · 研究领域：Congenital heart defects research

During development of the mammalian pituitary gland, specific hormone-producing cell types, critical in maintaining homeostasis, emerge in a spatially and temporally specific fashion from an ectodermal primordium. We have investigated the molecular basis of generating diverse cell phenotypes from a common precursor, providing in vivo and in vitro evidence that development of these cell types involves at least four sequential phases of signaling events and the action of a gradient at an ectodermal boundary. In the first phase, we hypothesize that this notochord induces invagination of Rathke's pouch from the oral ectoderm. This is followed by appearance of an ectodermal boundary, formed with exclusion of Shh from the nascent pouch. Next, signals from the ventral diencephalon--expressing BMP4, Wnt5a, FGF10, and FGF8--in concert with Shh represent critical in vivo signals for pituitary determination. Subsequently, a dorsal-ventral BMP2 signal gradient emanates from a ventral pituitary organizing center, forming at the boundary to oral ectoderm region from which Shh expression is selectively excluded. In concert with a dorsal FGF8 signal, this creates opposing gradients that generate overlapping patterns of specific transcription factors that underlie cell lineage specification events. The mechanisms by which these transient gradients of signaling molecules lead to the appearance of four ventral pituitary cell types appear to involve the reciprocal interactions of two transcripti...