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Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, Université de Lyon, UMR INRA CNRS 5242, IFR128 46 allée dItalie, 69364 Lyon Cedex 07, France
1 Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) and Center for Biomedical Research on Rare Diseases (CIBERER), 28029 Madrid, Spain
2 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
3 Cancer Genetics Branch, NHGRI, Bethesda, Maryland, USA
4 Institut de recherche en Immunologie et Cancer, Université de Montréal, Montréal H3C3J7, Quebec, Canada
(Requests for offprints should be addressed to F Flamant; Email: frederic.flamant{at}ens-lyon.fr)
Thyroid hormones act directly on gene transcription in the post-natal developing cerebellum, controlling neuronal, and glial cell differentiation. We have combined three experimental approaches to identify the target genes that are underlying this phenomenon: 1) a microarray analysis of gene expression to identify hormone responsive genes in the cerebellum of Pax8/ mice, a transgenic mouse model of congenital hypothyroidism; 2) a similar microarray analysis on primary culture of cerebellum neurons; and 3) a bioinformatics screen of conserved putative-binding sites in the mouse genome. This identifies surprisingly a small set of target genes, which, for some of them, might be key regulators of cerebellum development and neuronal differentiation.
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