TY - JOUR
T1 - TTF-1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion
AU - Lee, Byung Ju
AU - Cho, Gyeong J.
AU - Norgren, Robert B.
AU - Junier, Marie Pierre
AU - Hill, Diane F.
AU - Tapia, Veronica
AU - Costa, Maria E.
AU - Ojeda, Sergio R.
N1 - Funding Information:
This work was supported by NIH Grants HD25123 (to S.R.O.), NS01719 (to R.B.N.), RR00163 for the operation of the Oregon Regional Primate Research Center, The Korea Ministry of Science & Technology (98-J04-02-01-A-06) (to B.J.L.), and Human Frontier Science Program (to M.P.J.). We thank Janie Gliessman for her editorial assistance.
PY - 2001
Y1 - 2001
N2 - TTF-1 is a member of the Nkx family of homeodomain genes required for morphogenesis of the hypothalamus. Whether TTF-1, or other Nkx genes, contributes to regulating differentiated hypothalamic functions is not known. We now report that postnatal hypothalamic TTF-1 expression is developmentally regulated and associated with the neuroendocrine process of female sexual development. Lesions of the hypothalamus that cause sexual precocity transiently activate neuronal TTF-1 expression near the lesion site. In intact animals, hypothalamic TTF-1 mRNA content also increases transiently, preceding the initiation of puberty. Postnatal expression of the TTF-1 gone was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and proproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothamamus, which restrain sexual maturation and facilitate reproductive behavior. TTF-1 mRNA was also detected in astrocytes of the median eminence and ependymal/subependymal cells of the third ventricle, where it colocalized with erbB-2, a receptor involved in facilitating sexual development. TTF-1 binds to and transactivates the erbB-2 and LHRH promoters, but represses transcription of the preproenkephalin gene. The singular increase in hypothalamic TTF-1 gene expression that precedes the initiation of puberty, its highly specific pattern of cellular expression, and its transcriptional actions on genes directly involved in neuroendocrine reproductive regulation suggest that TTF-1 may represent one of the controlling factors that set in motion early events underlying the central activation of mammalian puberty.
AB - TTF-1 is a member of the Nkx family of homeodomain genes required for morphogenesis of the hypothalamus. Whether TTF-1, or other Nkx genes, contributes to regulating differentiated hypothalamic functions is not known. We now report that postnatal hypothalamic TTF-1 expression is developmentally regulated and associated with the neuroendocrine process of female sexual development. Lesions of the hypothalamus that cause sexual precocity transiently activate neuronal TTF-1 expression near the lesion site. In intact animals, hypothalamic TTF-1 mRNA content also increases transiently, preceding the initiation of puberty. Postnatal expression of the TTF-1 gone was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and proproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothamamus, which restrain sexual maturation and facilitate reproductive behavior. TTF-1 mRNA was also detected in astrocytes of the median eminence and ependymal/subependymal cells of the third ventricle, where it colocalized with erbB-2, a receptor involved in facilitating sexual development. TTF-1 binds to and transactivates the erbB-2 and LHRH promoters, but represses transcription of the preproenkephalin gene. The singular increase in hypothalamic TTF-1 gene expression that precedes the initiation of puberty, its highly specific pattern of cellular expression, and its transcriptional actions on genes directly involved in neuroendocrine reproductive regulation suggest that TTF-1 may represent one of the controlling factors that set in motion early events underlying the central activation of mammalian puberty.
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U2 - 10.1006/mcne.2000.0933
DO - 10.1006/mcne.2000.0933
M3 - Article
C2 - 11161473
AN - SCOPUS:0035155013
SN - 1044-7431
VL - 17
SP - 107
EP - 126
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 1
ER -