title: Transcriptional control of cell phenotypes in the neuroendocrine system.
abstract: A fundamental aspect of the development of complex organ systems is a requirement for precise temporal and spatial coordination in the genesis of tissues of distinct embryonic origins, in order to form functional units required for physiological homeostasis and survival. Such a requirement is particularly well exemplified in mammalian development in the formation of the hypothalamic-pituitary axis. Neuronally expressed POU domain factors might exert effects on terminal differentiation events similar to those of Pit-1 in the maturation of anterior pituitary gland cell phenotypes. Neurons comprising the endocrine hypothalamus develop in tandem with their ultimate target, the pituitary gland, and arise from a primordium in which three related class III POU domain factors-Brn-2, Brn-4, and Brn-1-are initially co-expressed. These factors subsequently exhibit stratified patterns of ontogenic expression, correlating with the appearance of distinct neuropeptides that define three major endocrine hypothalamic cell types. Deletion of the Brn-2 genomic locus affects terminal differentiation and/or maintenance of hypothalamic neurosecretory neurons and development of the posterior pituitary gland. Thus, both neuronal and endocrine components of the hypothalamic-pituitary axis are critically dependent upon the action of specific POU domain factors at a penultimate step in the sequential events that underlie the appearance of mature cellular phenotypes.
authors.affiliation: Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, La Jolla 92093-0648, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Rosenfeld
authors.forename: I
authors.initials: I
authors.lastname: Bach
authors.forename: L
authors.initials: L
authors.lastname: Erkman
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.forename: R
authors.initials: R
authors.lastname: McEvilly
authors.forename: A
authors.initials: A
authors.lastname: Ryan
authors.forename: S
authors.initials: S
authors.lastname: Rhodes
authors.forename: M
authors.initials: M
authors.lastname: Schonnemann
authors.forename: K
authors.initials: K
authors.lastname: Scully
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009490:Neurosecretory Systems / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D050809:POU Domain Factors; D010641:Phenotype; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D050809:POU Domain Factors; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D014157:Transcription Factors