title: Thyroid hormone signaling during early neurogenesis and its significance as a vulnerable window for endocrine disruption.
abstract: The essential roles of thyroid hormone (TH) in perinatal brain development have been known for decades. More recently, many of the molecular mechanisms underlying the multiple effects of TH on proliferation, differentiation, migration, synaptogenesis and myelination in the developing nervous system have been elucidated. At the same time data from both epidemiological studies and animal models have revealed that the influence of thyroid signaling on development of the nervous system, extends to all periods of life, from early embryogenesis to neurogenesis in the adult brain. This review focuses on recent insights into the actions of TH during early neurogenesis. A key concept is that, in contrast to the previous ideas that only the unliganded receptor was implicated in these early phases, a critical role of the ligand, T3, is increasingly recognized. These findings are considered in the light of increasing knowledge of cell specific control of T3 availability as a function of deiodinase activity and transporter expression. These requirements for TH in the early stages of neurogenesis take on new relevance given the increasing epidemiological data on adverse effects of TH lack in early pregnancy on children's neurodevelopmental outcome. These ideas lead logically into a discussion on how the actions of TH during the first phases of neurogenesis can be potentially disrupted by gestational iodine lack and/or chemical pollution. This article is part of a Special Issue entitled: Nuclear receptors in animal development.
authors: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 75231 Paris, France.
authors: Laetitia
authors: L
authors: Préau
authors: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 75231 Paris, France.
authors: Jean Baptiste
authors: JB
authors: Fini
authors: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 75231 Paris, France.
authors: Ghislaine
authors: G
authors: Morvan-Dubois
authors: UMR CNRS 7221, Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 75231 Paris, France. Electronic address: bdem@mnhn.fr.
authors: Barbara
authors: B
authors: Demeneix
mesh_terms: D000328:Adult; D000818:Animals; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D006801:Humans; D023421:Models, Animal; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D011247:Pregnancy; D011988:Receptors, Thyroid Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013963:Thyroid Hormones / Q000494:pharmacology / Q000502:physiology*
chemical_list: D052244:Endocrine Disruptors; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones
keywords: Disruptors; Embryogenesis; Neurodevelopment; Neurogenesis; Thyroid hormones