TTF-1, a Homeodomain Gene Required for Diencephalic Morphogenesis, Is Postnatally Expressed in the Neuroendocrine Brain in a Developmentally Regulated and Cell-Specific Fashion
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 regu...
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description | 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 gene was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and preproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothalamus, 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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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 gene was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and preproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothalamus, 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.</description><identifier>ISSN: 1044-7431</identifier><identifier>EISSN: 1095-9327</identifier><identifier>DOI: 10.1006/mcne.2000.0933</identifier><identifier>PMID: 11161473</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aging - metabolism ; Animals ; Astrocytes - cytology ; Astrocytes - metabolism ; Cell Line ; Diencephalon - cytology ; Diencephalon - embryology ; Diencephalon - metabolism ; Enkephalins - genetics ; Enkephalins - metabolism ; Ependyma - cytology ; Ependyma - metabolism ; Female ; Gene Expression Regulation, Developmental ; Gene Silencing ; Gonadotropin-Releasing Hormone - genetics ; Gonadotropin-Releasing Hormone - metabolism ; Hypothalamus - cytology ; Hypothalamus - metabolism ; Hypothalamus - surgery ; Median Eminence - cytology ; Median Eminence - metabolism ; Neurons - classification ; Neurons - cytology ; Neurons - metabolism ; Neurosecretory Systems - cytology ; Neurosecretory Systems - metabolism ; Nuclear Proteins - biosynthesis ; Nuclear Proteins - genetics ; Nuclear Proteins - pharmacology ; Promoter Regions, Genetic - drug effects ; Protein Precursors - genetics ; Protein Precursors - metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, ErbB-2 - genetics ; Receptor, ErbB-2 - metabolism ; RNA, Messenger - metabolism ; Thyroid Gland - cytology ; Thyroid Gland - metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Transcription Factors - pharmacology ; Transcriptional Activation ; TTF-1 gene</subject><ispartof>Molecular and cellular neuroscience, 2001-01, Vol.17 (1), p.107-126</ispartof><rights>2001 Academic Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-9534835b1e4b42c73e94bee233079251dd3656e7b3a1ec8155e4f27a9fd73af23</citedby><cites>FETCH-LOGICAL-c371t-9534835b1e4b42c73e94bee233079251dd3656e7b3a1ec8155e4f27a9fd73af23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/mcne.2000.0933$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11161473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Byung Ju</creatorcontrib><creatorcontrib>Cho, Gyeong J.</creatorcontrib><creatorcontrib>Norgren, Robert B.</creatorcontrib><creatorcontrib>Junier, Marie Pierre</creatorcontrib><creatorcontrib>Hill, Diane F.</creatorcontrib><creatorcontrib>Tapia, Veronica</creatorcontrib><creatorcontrib>Costa, Maria E.</creatorcontrib><creatorcontrib>Ojeda, Sergio R.</creatorcontrib><title>TTF-1, a Homeodomain Gene Required for Diencephalic Morphogenesis, Is Postnatally Expressed in the Neuroendocrine Brain in a Developmentally Regulated and Cell-Specific Fashion</title><title>Molecular and cellular neuroscience</title><addtitle>Mol Cell Neurosci</addtitle><description>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 gene was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and preproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothalamus, 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.</description><subject>Aging - metabolism</subject><subject>Animals</subject><subject>Astrocytes - cytology</subject><subject>Astrocytes - metabolism</subject><subject>Cell Line</subject><subject>Diencephalon - cytology</subject><subject>Diencephalon - embryology</subject><subject>Diencephalon - metabolism</subject><subject>Enkephalins - genetics</subject><subject>Enkephalins - metabolism</subject><subject>Ependyma - cytology</subject><subject>Ependyma - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gene Silencing</subject><subject>Gonadotropin-Releasing Hormone - genetics</subject><subject>Gonadotropin-Releasing Hormone - metabolism</subject><subject>Hypothalamus - cytology</subject><subject>Hypothalamus - metabolism</subject><subject>Hypothalamus - surgery</subject><subject>Median Eminence - cytology</subject><subject>Median Eminence - metabolism</subject><subject>Neurons - classification</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>Neurosecretory Systems - cytology</subject><subject>Neurosecretory Systems - metabolism</subject><subject>Nuclear Proteins - biosynthesis</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - pharmacology</subject><subject>Promoter Regions, Genetic - drug effects</subject><subject>Protein Precursors - genetics</subject><subject>Protein Precursors - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Thyroid Gland - cytology</subject><subject>Thyroid Gland - metabolism</subject><subject>Thyroid Nuclear Factor 1</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - pharmacology</subject><subject>Transcriptional Activation</subject><subject>TTF-1 gene</subject><issn>1044-7431</issn><issn>1095-9327</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAURSNERUthyxJ5xaoZ7DwnTpYw7bSVWkBlWFuO_dIxSuzUTqr2r_hEHGYkVgjJkr04974nnyx7x-iKUVp9HLTDVUEpXdEG4EV2wmhT5g0U4uXy5jwXHNhx9jrGn4kqiwZeZceMsYpxASfZr-12k7MzosiVH9AbPyjryCU6JHf4MNuAhnQ-kHOLTuO4U73V5NaHcefvExRtPCPXkXzzcXJqUn3_TC6exoAxpmBqmnZIvuAcPDrjdbCp93NYRqSjyDk-Yu_HAd0-eof3c6-mFFXOkDX2ff59RG27NHSj4s569yY76lQf8e3hPs1-bC6266v85uvl9frTTa5BsClvSuA1lC1D3vJCC8CGt4gFABVNUTJjoCorFC0ohrpmZYm8K4RqOiNAdQWcZh_2vWPwDzPGSQ426rSRcujnKAWtoKYM_gsyUTMONUvgag_q4GMM2Mkx2EGFZ8moXGTKRaZcZMpFZgq8PzTP7YDmL36wl4B6D2D6iEeLQUb9x5NJ3vQkjbf_6v4NRXGvkQ</recordid><startdate>200101</startdate><enddate>200101</enddate><creator>Lee, Byung Ju</creator><creator>Cho, Gyeong J.</creator><creator>Norgren, Robert B.</creator><creator>Junier, Marie Pierre</creator><creator>Hill, Diane F.</creator><creator>Tapia, Veronica</creator><creator>Costa, Maria E.</creator><creator>Ojeda, Sergio R.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>200101</creationdate><title>TTF-1, a Homeodomain Gene Required for Diencephalic Morphogenesis, Is Postnatally Expressed in the Neuroendocrine Brain in a Developmentally Regulated and Cell-Specific Fashion</title><author>Lee, Byung Ju ; Cho, Gyeong J. ; Norgren, Robert B. ; Junier, Marie Pierre ; Hill, Diane F. ; Tapia, Veronica ; Costa, Maria E. ; Ojeda, Sergio R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-9534835b1e4b42c73e94bee233079251dd3656e7b3a1ec8155e4f27a9fd73af23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Aging - metabolism</topic><topic>Animals</topic><topic>Astrocytes - cytology</topic><topic>Astrocytes - metabolism</topic><topic>Cell Line</topic><topic>Diencephalon - cytology</topic><topic>Diencephalon - embryology</topic><topic>Diencephalon - metabolism</topic><topic>Enkephalins - genetics</topic><topic>Enkephalins - metabolism</topic><topic>Ependyma - cytology</topic><topic>Ependyma - metabolism</topic><topic>Female</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gene Silencing</topic><topic>Gonadotropin-Releasing Hormone - genetics</topic><topic>Gonadotropin-Releasing Hormone - metabolism</topic><topic>Hypothalamus - cytology</topic><topic>Hypothalamus - metabolism</topic><topic>Hypothalamus - surgery</topic><topic>Median Eminence - cytology</topic><topic>Median Eminence - metabolism</topic><topic>Neurons - classification</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>Neurosecretory Systems - cytology</topic><topic>Neurosecretory Systems - metabolism</topic><topic>Nuclear Proteins - biosynthesis</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - pharmacology</topic><topic>Promoter Regions, Genetic - drug effects</topic><topic>Protein Precursors - genetics</topic><topic>Protein Precursors - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Thyroid Gland - cytology</topic><topic>Thyroid Gland - metabolism</topic><topic>Thyroid Nuclear Factor 1</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - pharmacology</topic><topic>Transcriptional Activation</topic><topic>TTF-1 gene</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Byung Ju</creatorcontrib><creatorcontrib>Cho, Gyeong J.</creatorcontrib><creatorcontrib>Norgren, Robert B.</creatorcontrib><creatorcontrib>Junier, Marie Pierre</creatorcontrib><creatorcontrib>Hill, Diane F.</creatorcontrib><creatorcontrib>Tapia, Veronica</creatorcontrib><creatorcontrib>Costa, Maria E.</creatorcontrib><creatorcontrib>Ojeda, Sergio R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Byung Ju</au><au>Cho, Gyeong J.</au><au>Norgren, Robert B.</au><au>Junier, Marie Pierre</au><au>Hill, Diane F.</au><au>Tapia, Veronica</au><au>Costa, Maria E.</au><au>Ojeda, Sergio R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TTF-1, a Homeodomain Gene Required for Diencephalic Morphogenesis, Is Postnatally Expressed in the Neuroendocrine Brain in a Developmentally Regulated and Cell-Specific Fashion</atitle><jtitle>Molecular and cellular neuroscience</jtitle><addtitle>Mol Cell Neurosci</addtitle><date>2001-01</date><risdate>2001</risdate><volume>17</volume><issue>1</issue><spage>107</spage><epage>126</epage><pages>107-126</pages><issn>1044-7431</issn><eissn>1095-9327</eissn><abstract>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 gene was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and preproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothalamus, 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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11161473</pmid><doi>10.1006/mcne.2000.0933</doi><tpages>20</tpages></addata></record> |
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subjects | Aging - metabolism Animals Astrocytes - cytology Astrocytes - metabolism Cell Line Diencephalon - cytology Diencephalon - embryology Diencephalon - metabolism Enkephalins - genetics Enkephalins - metabolism Ependyma - cytology Ependyma - metabolism Female Gene Expression Regulation, Developmental Gene Silencing Gonadotropin-Releasing Hormone - genetics Gonadotropin-Releasing Hormone - metabolism Hypothalamus - cytology Hypothalamus - metabolism Hypothalamus - surgery Median Eminence - cytology Median Eminence - metabolism Neurons - classification Neurons - cytology Neurons - metabolism Neurosecretory Systems - cytology Neurosecretory Systems - metabolism Nuclear Proteins - biosynthesis Nuclear Proteins - genetics Nuclear Proteins - pharmacology Promoter Regions, Genetic - drug effects Protein Precursors - genetics Protein Precursors - metabolism Rats Rats, Sprague-Dawley Receptor, ErbB-2 - genetics Receptor, ErbB-2 - metabolism RNA, Messenger - metabolism Thyroid Gland - cytology Thyroid Gland - metabolism Thyroid Nuclear Factor 1 Transcription Factors - biosynthesis Transcription Factors - genetics Transcription Factors - pharmacology Transcriptional Activation TTF-1 gene |
title | TTF-1, a Homeodomain Gene Required for Diencephalic Morphogenesis, Is Postnatally Expressed in the Neuroendocrine Brain in a Developmentally Regulated and Cell-Specific Fashion |
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