Skip to main content
Log in

Cloning and developmental expression of five estrogen-receptor related genes in the zebrafish

  • Original Article
  • Published:
Development Genes and Evolution Aims and scope Submit manuscript

Abstract

Estrogen-receptor related receptors (ERRα, β and γ) are so-called orphan (i.e. for which no natural ligand has been identified to date) nuclear receptors that are closely related to the estrogen receptors. To gain insights into the possible functions of ERRs during early development, we have cloned their homologs in the zebrafish. Five err cDNA types were recovered in a PCR screen. Transient transfection experiments indicated that zebrafish ERRα, ERRγ and ERRδ display transcriptional activities that are identical to those of their mammalian counterparts. The expression patterns of err genes were determined during zebrafish development. Tissues such as the hindbrain or the pronephric tubes express several errs whereas others, such as the presumptive mesoderm at the level of the margin, specifically express a single err. Our analysis also points to tissues in which err expression is conserved through evolution, such as slow muscles that specifically express errα, suggesting important functions in these tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1a, b
Fig. 2a, b
Fig. 3a–k
Fig. 4a–d
Fig. 5a–f
Fig. 6a–f

Similar content being viewed by others

References

  • Ariazi EA, Clark GM, Mertz JE (2002) Estrogen-related receptor α and estrogen-related receptor γ associate with unfavorable and favorable biomarkers, respectively, in human breast cancer. Cancer Res 62:6510–6518

    CAS  PubMed  Google Scholar 

  • Bardet P-L, Horard B, Robinson-Rechavi M, Laudet V, Vanacker J-M (2002) Characterization of œstrogen receptors in zebrafish (Danio rerio). J Mol Endocrinol 28:153–163

    CAS  PubMed  Google Scholar 

  • Bonnelye E, Vanacker JM, Spruyt N, Alric S, Fournier B, Desbiens X, Laudet V (1997a) Expression of the estrogen-related receptor 1 (ERR-1) orphan receptor during mouse development. Mech Dev 65:71–85

    Article  CAS  Google Scholar 

  • Bonnelye E, Vanacker JM, Dittmar T, Begue A, Desbiens X, Denhardt DT, Aubin JE, Laudet V, Fournier B (1997b) The ERR-1 orphan receptor is a transcriptional activator expressed during bone development. Mol Endocrinol 11:905–916

    Article  CAS  Google Scholar 

  • Bonnelye E, Merdad L, Kung V, Aubin JE (2001) The orphan nuclear estrogen receptor-related receptor alpha (ERRalpha) is expressed throughout osteoblast differentiation and regulates bone formation in vitro. J Cell Biol 153:971–984

    Article  CAS  PubMed  Google Scholar 

  • Coward P, Lee D, Hull MV, Lehmann JM (2001) 4-Hydroxytamoxifen binds to and deactivates the estrogen-related receptor gamma. Proc Natl Acad Sci USA 98:8880–8884

    Article  CAS  PubMed  Google Scholar 

  • Dehal et al (2002) The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298:2157–2167

    Article  CAS  PubMed  Google Scholar 

  • Devoto SH, Melançon E, Eisen JS, Westerfeld M (1996) Identification of separate slow and fast muscle precursor cells, in vivo, prior to somite formation. Development 122:3371–3380

    CAS  PubMed  Google Scholar 

  • Escriva H, Safi R, Hanni C, Langlois MC, Saumitou-Laprade P, Stehelin D, Capron A, Pierce R, Laudet V (1997) Ligand binding was acquired during evolution of nuclear receptors. Proc Natl Acad Sci USA 94:6803–6808

    PubMed  Google Scholar 

  • Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791

    Google Scholar 

  • Galtier N, Gouy M, Gautier C (1996) SEAVIEW and PHYLO_WIN: two graphic tools for sequence alignment and molecular phylogeny. Comput Appl Biosci 12:543–548

    CAS  PubMed  Google Scholar 

  • Giguère V (1999) Orphan nuclear receptors: from gene to function. Endocr Rev 20:689–725

    Article  Google Scholar 

  • Giguère V (2002) To ERR in the estrogen pathway. Trends Endocrinol Metab 13:220–225

    Article  PubMed  Google Scholar 

  • Giguère V, Yang N, Segui P, Evans RM (1988) Identification of a new class of steroid hormone receptors. Nature 331:91–94

    Article  PubMed  Google Scholar 

  • Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP (2002) Structural and functional evidence for ligand-independent transcriptional activation by the Estrogen-Related Receptor 3. Mol Cell 9:303–313

    CAS  PubMed  Google Scholar 

  • Hermans-Borgmeyer I, Susens U, Borgmeyer U (2000) Developmental expression of the estrogen receptor-related receptor gamma in the nervous system during mouse embryogenesis. Mech Dev 97:197–199

    Article  CAS  PubMed  Google Scholar 

  • Hong H, Yang L, Stallcup MR (1999) Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3. J Biol Chem 274:22618–22626

    Article  CAS  PubMed  Google Scholar 

  • Horard B, Vanacker JM (2003) Estrogen receptor-related receptors: orphan receptors desperately seeking a ligand. J Mol Endocrinol 31:349–357

    CAS  PubMed  Google Scholar 

  • Ichida M, Nemoto S, Finkel T (2002) Identification of a specific molecular repressor of the nuclear coactivator PGC-1alpha. J Biol Chem 277:50991–50995

    Article  CAS  PubMed  Google Scholar 

  • Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203:253–310

    CAS  PubMed  Google Scholar 

  • Kraus RJ, Ariazi EA, Farrell ML, Mertz JE (2002) Estrogen-related receptor α1 actively antagonizes estrogen receptor-regulated transcription in MCF-7 mammary cells. J Biol Chem 277:24826–24834

    Article  CAS  PubMed  Google Scholar 

  • Laudet V (1997) Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor. J Mol Endocrinol 19:207–226

    CAS  PubMed  Google Scholar 

  • Laudet V, Gronemeyer H (2002) The nuclear receptor facts book. Academic, San Diego

  • Luo J, Sladek R, Bader JA, Matthyssen A, Rossant J, Giguere V (1997) Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta. Nature 388:778–782

    Article  CAS  Google Scholar 

  • Luo J, Sladek R, Carrier J, Bader JA, Richard D, Giguère V (2003) Reduced fat mass in mice lacking orphan nuclear receptor Estrogen-Related Receptor α. Mol Cell Biol 23:7947–7956

    Article  CAS  Google Scholar 

  • Nuclear Receptor Nomenclature Committee (1999) A unified nomenclature system for the nuclear receptor superfamily. Cell 97:161–163

    PubMed  Google Scholar 

  • Pettersson K, Svensson K, Mattsson R, Carlsson B, Ohlsson R, Berkenstam A (1996) Expression of a novel member of estrogen response element-binding nuclear receptors is restricted to the early stages of chorion formation during mouse embryogenesis. Mech Dev 54:211–223

    Article  CAS  PubMed  Google Scholar 

  • Robinson-Rechavi M, Marchand O, Escriva H, Laudet V (2001a) An ancestral whole-genome duplication may not have been responsible for the abundance of duplicated fish genes. Curr Biol 11:R458–R459

    CAS  PubMed  Google Scholar 

  • Robinson-Rechavi M, Marchand O, Escriva H, Bardet P-L, Zelus D, Hughes S, Laudet V (2001b) Euteleost fish genomes are characterized by expansion of gene families. Genome Res 11:781–788

    CAS  PubMed  Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    CAS  PubMed  Google Scholar 

  • Sluder AE, Maina CV (2001) Nuclear receptors in nematode: themes and variations. Trends Genet 17:206–213

    Article  CAS  PubMed  Google Scholar 

  • Sluder AE, Mathews SW, Hough D, Yin VP, Maina CV (1999) The nuclear receptor superfamily has undergone extensive proliferation and diversification in nematodes. Genome Res 9:103–120

    CAS  PubMed  Google Scholar 

  • Sullivan AA, Thummel CS (2003) Temporal profiles of nuclear receptor gene expression reveal coordinate transcriptional responses during Drosophila development. Mol Endocrinol 17(11):2125–2137

    Article  CAS  PubMed  Google Scholar 

  • Thisse C, Thisse B, Schilling TF, Postlethwait JH (1993) Structure of the zebrafish snail1 gene and its expression in wild-type, spadetail and no tail mutant embryos. Development 119:1203–1215

    CAS  PubMed  Google Scholar 

  • Thomson JD, Higgins DG and Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680

    PubMed  Google Scholar 

  • Vanacker J-M, Bonnelye E, Delmarre C, Laudet V (1998) Activation of the thyroid hormone receptor alpha gene promoter by the orphan nuclear receptor ERR alpha. Oncogene 17:2429–2435

    Article  CAS  PubMed  Google Scholar 

  • Vanacker JM, Pettersson K, Gustafsson JÅ, Laudet V (1999a) Transcriptional targets shared by estrogen receptor-related receptors (ERRs) and estrogen receptor (ER)α, but not by ERβ. EMBO J 18:4270–4279

    Article  CAS  Google Scholar 

  • Vanacker J-M, Bonnelye E, Chopin-Delannoy S, Delmarre C, Cavaillès V, Laudet V (1999b) Transcriptional activities of the orphan nuclear receptor ERRα. Mol Endocrinol 13:764–773

    Article  CAS  PubMed  Google Scholar 

  • Vega RB, Kelly DP (1997) A role for estrogen-related receptor alpha in the control of mitochondrial fatty acid beta-oxidation during brown adipocyte differentiation. J Biol Chem 272:31693–31699

    Article  CAS  Google Scholar 

  • Xie W, Hong H, Yang NN, Lin RJ, Simon CM, Stallcup MR, Evans RM (1999) Constitutive activation of transcription and binding of coactivator by Estrogen-Related Receptors 1 and 2. Mol Endocrinol 13:2151–2162

    Article  CAS  PubMed  Google Scholar 

  • Yang N, Shigeta H, Shi H, Teng CT (1996) Estrogen-related receptor, hERR1, modulates estrogen receptor-mediated response of human lactoferrin gene promoter. J Biol Chem 271:5795–5804

    Article  CAS  Google Scholar 

  • Zhang Z, Teng CT (2000) Estrogen receptor-related receptor α1 interacts with coactivator and constitutively activates the estrogen response elements of the human lactoferrin gene. J Biol Chem 275:20837–20846

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the Centre National de la Recherche Scientifique (CNRS), Ecole Normale Supérieure de Lyon, Région Rhône-Alpes, Ligue contre le Cancer (comités Ardèche, Drôme and Loire) and Proskelia Pharmaceuticals (Romainville) for financial support. We thank Marc Robinson-Rechavi for help with gene phylogeny.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vincent Laudet.

Additional information

Edited by D. Tautz

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bardet, PL., Obrecht-Pflumio, S., Thisse, C. et al. Cloning and developmental expression of five estrogen-receptor related genes in the zebrafish. Dev Genes Evol 214, 240–249 (2004). https://doi.org/10.1007/s00427-004-0404-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00427-004-0404-6

Keywords

Navigation