title: Purkinje cells and Bergmann glia are primary targets of the TRα1 thyroid hormone receptor during mouse cerebellum postnatal development.
abstract: Thyroid hormone is necessary for normal development of the central nervous system, as shown by the severe mental retardation syndrome affecting hypothyroid patients with low levels of active thyroid hormone. The postnatal defects observed in hypothyroid mouse cerebellum are recapitulated in mice heterozygous for a dominant-negative mutation of Thra, the gene encoding the ubiquitous TRα1 receptor. Using CRE/loxP-mediated conditional expression approach, we found that this mutation primarily alters the differentiation of Purkinje cells and Bergmann glia, two cerebellum-specific cell types. These primary defects indirectly affect cerebellum development in a global manner. Notably, the inward migration and terminal differentiation of granule cell precursors is impaired. Therefore, despite the broad distribution of its receptors, thyroid hormone targets few cell types that exert a predominant role in the network of cellular interactions that govern normal cerebellum maturation.
authors.affiliation: Université de Lyon, CNRS, INRA, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon, Institut de Génomique Fonctionnelle de Lyon, F-69364 Lyon, Cedex 07, France.
authors.forename: Teddy
authors.initials: T
authors.lastname: Fauquier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chatonnet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Picou
authors.forename: Sabine
authors.initials: S
authors.lastname: Richard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fossat
authors.forename: Nadine
authors.initials: N
authors.lastname: Aguilera
authors.forename: Thomas
authors.initials: T
authors.lastname: Lamonerie
authors.forename: Frédéric
authors.initials: F
authors.lastname: Flamant
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005136:Eye Proteins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis; D011689:Purkinje Cells / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D037021:Thyroid Hormone Receptors alpha; D014284:Triiodothyronine
keywords: Cerebellum; Mouse; Thyroid hormone receptor