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Several animal models have been used to investigate this function, including mice heterozygous for the TR\u03b11R384C mutation, which confers receptor-mediated hypothyroidism. These mice display abnormalities in several autonomic functions, which was partially attributed to a developmental defect in hypothalamic parvalbumin neurons. However, whether other cell types in the hypothalamus are similarly affected remains unknown. Here, we used single-nucleus RNA sequencing to obtain an unbiased view on the importance of TR\u03b11 for hypothalamic development and cellular diversity. Our data show that defective TR\u03b11 signaling has surprisingly little effect on the development of hypothalamic neuronal populations, but it heavily affects hypothalamic oligodendrocytes. Using selective reactivation of the mutant TR\u03b11 during specific developmental periods, we find that early postnatal thyroid hormone action seems to be crucial for proper hypothalamic oligodendrocyte maturation. Taken together, our findings underline the well-known importance of postnatal thyroid health for brain development and provide an unbiased roadmap for the identification of cellular targets of TR\u03b11 action in mouse hypothalamic development.<\/jats:p>","DOI":"10.1242\/dev.201228","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T08:58:43Z","timestamp":1675069123000},"source":"Crossref","is-referenced-by-count":16,"title":["Single-cell RNA-based phenotyping reveals a pivotal role of thyroid hormone receptor alpha for hypothalamic development"],"prefix":"10.1242","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-8394","authenticated-orcid":false,"given":"Varun K. A.","family":"Sreenivasan","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Schleswig-Holstein, University of L\u00fcbeck and University of Kiel 1 , L\u00fcbeck 23562 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Dore","sequence":"additional","affiliation":[{"name":"Institute for Endocrinology and Diabetes, University of L\u00fcbeck and Universit\u00e4tsklinikum Schleswig-Holstein Campus L\u00fcbeck, Center of Brain Behavior and Metabolism (CBBM) 2 , Ratzeburger Allee 160, 23562 L\u00fcbeck , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Resch","sequence":"additional","affiliation":[{"name":"Institute for Endocrinology and Diabetes, University of L\u00fcbeck and Universit\u00e4tsklinikum Schleswig-Holstein Campus L\u00fcbeck, Center of Brain Behavior and Metabolism (CBBM) 2 , Ratzeburger Allee 160, 23562 L\u00fcbeck , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Maier","sequence":"additional","affiliation":[{"name":"Institute for Endocrinology and Diabetes, University of L\u00fcbeck and Universit\u00e4tsklinikum Schleswig-Holstein Campus L\u00fcbeck, Center of Brain Behavior and Metabolism (CBBM) 2 , Ratzeburger Allee 160, 23562 L\u00fcbeck , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Human Molecular Genomics Group, Max Planck Institute for Molecular Genetics 3 , Berlin 14195 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Henck","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Schleswig-Holstein, University of L\u00fcbeck and University of Kiel 1 , L\u00fcbeck 23562 , Germany"},{"name":"Human Molecular Genomics Group, Max Planck Institute for Molecular Genetics 3 , Berlin 14195 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranya","family":"Balachandran","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Schleswig-Holstein, University of L\u00fcbeck and University of Kiel 1 , L\u00fcbeck 23562 , Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), partner site Hamburg\/L\u00fcbeck\/Kiel 4 , L\u00fcbeck 23562 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7778-5158","authenticated-orcid":false,"given":"Jens","family":"Mittag","sequence":"additional","affiliation":[{"name":"Institute for Endocrinology and Diabetes, University of L\u00fcbeck and Universit\u00e4tsklinikum Schleswig-Holstein Campus L\u00fcbeck, Center of Brain Behavior and Metabolism (CBBM) 2 , Ratzeburger Allee 160, 23562 L\u00fcbeck , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-4683","authenticated-orcid":false,"given":"Malte","family":"Spielmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Schleswig-Holstein, University of L\u00fcbeck and University of Kiel 1 , L\u00fcbeck 23562 , Germany"},{"name":"Human Molecular Genomics Group, Max Planck Institute for Molecular Genetics 3 , Berlin 14195 , Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), partner site Hamburg\/L\u00fcbeck\/Kiel 4 , L\u00fcbeck 23562 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"2023013008574715700_DEV201228C1","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/S0022-3476(89)80292-6","article-title":"Changes in brain maturation detected by magnetic resonance imaging in congenital hypothyroidism","volume":"115","author":"Alves","year":"1989","journal-title":"J. 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