title: Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche.
abstract: The subventricular zone (SVZ) neural stem cell niche contains mixed populations of stem cells, transit-amplifying cells, and migrating neuroblasts. Deciphering how endogenous signals, such as hormones, affect the balance between these cell types is essential for understanding the physiology of niche plasticity and homeostasis. We show that Thyroid Hormone (T(3)) and its receptor, TRα1, are directly involved in maintaining this balance. TRα1 is expressed in amplifying and migrating cells. In vivo gain- and loss-of-function experiments demonstrate first, that T(3)/TRα1 directly repress Sox2 expression, and second, that TRα1 overexpression in the niche favors the appearance of DCX+ migrating neuroblasts. Lack of TRα increases numbers of SOX2+ cells in the SVZ. Hypothyroidism increases proportions of cells in interphase. Thus, in the adult SVZ, T(3)/TRα1 together favor neural stem cell commitment and progression toward a migrating neuroblast phenotype; this transition correlates with T(3)/TRα1-dependent transcriptional repression of Sox2.
authors.affiliation: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 75231 Paris, France.
authors.forename: Alejandra
authors.initials: A
authors.lastname: López-Juárez
authors.forename: Sylvie
authors.initials: S
authors.lastname: Remaud
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hassani
authors.forename: Pascale
authors.initials: P
authors.lastname: Jolivet
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Pierre Simons
authors.forename: Thomas
authors.initials: T
authors.lastname: Sontag
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Jack
authors.initials: J
authors.lastname: Price
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Morvan-Dubois
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Demeneix
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D000089662:Doublecortin Protein; D004794:Enzyme Repression / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000235:genetics; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones