title: Unexpected novel relational links uncovered by extensive developmental profiling of nuclear receptor expression.
abstract: Nuclear receptors (NRs) are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase PCR and/or DNA microarrays have been performed in classical model systems such as Drosophila and mouse, no systematic atlas describing NR involvement during embryonic development on a global scale has been assembled. Adopting a systems biology approach, we conducted a systematic analysis of the dynamic spatiotemporal expression of all NR genes as well as their main transcriptional coregulators during zebrafish development (101 genes) using whole-mount in situ hybridization. This extensive dataset establishes overlapping expression patterns among NRs and coregulators, indicating hierarchical transcriptional networks. This complete developmental profiling provides an unprecedented examination of expression of NRs during embryogenesis, uncovering their potential function during central nervous system and retina formation. Moreover, our study reveals that tissue specificity of hormone action is conferred more by the receptors than by their coregulators. Finally, further evolutionary analyses of this global resource led us to propose that neofunctionalization of duplicated genes occurs at the levels of both protein sequence and RNA expression patterns. Altogether, this expression database of NRs provides novel routes for leading investigation into the biological function of each individual NR as well as for the study of their combinatorial regulatory circuitry within the superfamily.
authors.affiliation: Molecular Zoology, Institut de Génomique Fonctionelle de Lyon; UMR 5242 du CNRS, INRA, IFR128 BioSciences Lyon-Gerland, Université de Lyon, UCB; Ecole Normale Supérieure de Lyon, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bertrand
authors.forename: Bernard
authors.initials: B
authors.lastname: Thisse
authors.forename: Raquel
authors.initials: R
authors.lastname: Tavares
authors.forename: Laurent
authors.initials: L
authors.lastname: Sachs
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chaumot
authors.forename: Pierre-Luc
authors.initials: PL
authors.lastname: Bardet
authors.forename: Héctor
authors.initials: H
authors.lastname: Escrivà
authors.forename: Maryline
authors.initials: M
authors.lastname: Duffraisse
authors.forename: Oriane
authors.initials: O
authors.lastname: Marchand
authors.forename: Rachid
authors.initials: R
authors.lastname: Safi
authors.forename: Christine
authors.initials: C
authors.lastname: Thisse
authors.forename: Vincent
authors.initials: V
authors.lastname: Laudet
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D018076:DNA, Complementary; D004625:Embryo, Nonmammalian / Q000196:embryology; D020440:Gene Duplication; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D010802:Phylogeny; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012160:Retina / Q000196:embryology / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors