Multistep signaling requirements for pituitary organogenesis in vivo

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 pituitary cell phenotype...

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Bibliographic Details
Published in:Genes & development 1998-06, Vol.12 (11), p.1691-1704
Main Authors: Treier, M, Gleiberman, A S, O'Connell, S M, Szeto, D P, McMahon, J A, McMahon, A P, Rosenfeld, M G
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Bone Morphogenetic Protein 2
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins - physiology
Embryonic and Fetal Development - physiology
Gene Expression Regulation, Developmental
Mice
Mice, Transgenic
Molecular Sequence Data
Pituitary Gland - embryology
Pituitary Gland - physiology
Research Paper
Signal Transduction - physiology
Transforming Growth Factor beta
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Summary: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 pituitary cell phenotypes from a common precursor, providing in vivo and in vitro evidence that their development involves three sequential phases of signaling events and the action of a gradient at an ectodermal boundary. In the first phase, the BMP4 signal from the ventral diencephalon, expressing BMP4, Wnt5a, and FGF8, represents a critical dorsal neuroepithelial signal for pituitary organ commitment in vivo. Subsequently, a BMP2 signal emanates from a ventral pituitary organizing center that forms at the boundary of a region of oral ectoderm in which Shh expression is selectively excluded. This BMP2 signal together with a dorsal FGF8 signal, appears to create opposing activity gradients that are suggested to generate overlapping patterns of specific transcription factors underlying cell lineage specification events, whereas Wnt4 is needed for the expansion of ventral pituitary cell phenotypes. In the third phase, temporally specific loss of the BMP2 signal is required to allow terminal differentiation. The consequence of these sequential organ and cellular determination events is that each of the hormone-producing pituitary cell types-gonadotropes, thyrotropes, somatotropes, lactotropes, corticotropes, and melanotropes-appear to be determined, in a ventral-to-dorsal gradient, respectively.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.12.11.1691