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Growth/differentiation factor-11: an evolutionary conserved growth factor in vertebrates

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Abstract

Growth and differentiation factor-11 (GDF-11) is a member of the transforming growth factor-β superfamily and is thought to be derived together with myostatin (known also as GDF-8) from an ancestral gene. In the present study, we report the isolation and characterization of GDF-11 homolog from a marine teleost, the gilthead sea bream Sparus aurata, and show that this growth factor is highly conserved throughout vertebrates. Using bioinformatics, we identified GDF-11 in Tetraodon, Takifugu, medaka, and stickleback and found that they are highly conserved at the amino acid sequence as well as gene organization. Moreover, we found conservation of syntenic relationships among vertebrates in the GDF-11 locus. Transcripts for GDF-11 can be found in eggs and early embryos, albeit at low levels, while in post-hatching larvae expression levels are high and decreases as development progresses, suggesting that GDF-11 might have a role during early development of fish as found in tetrapods and zebrafish. Finally, GDF-11 is expressed in various tissues in the adult fish including muscle, brain, and eye.

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References

  • Altschul SF, Madden TL, Schaeffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  CAS  PubMed  Google Scholar 

  • Biga PR, Roberts SB, Iliev DB, McCauley LAR, Moon JS, Collodi P, Goetz FW (2005) The isolation, characterization, and the expression of a novel GDF11 gene and a second myostatin from zebrafish, Danio rerio. Comp Biochem Physiol B Biochem Mol Biol 141:218–230

    Article  PubMed  Google Scholar 

  • Dichmann DS, Yassin H, Serup P (2006) Analysis of pancreatic endocrine development in GDF11-deficient mice. Dev Dyn 235:3016–3025

    Article  CAS  PubMed  Google Scholar 

  • Essalmani R, Zaid A, Marcinkiewicz J, Chamberland A, Pasquato A, Seidah NG, Prat A (2008) In vivo functions of the proprotein convertase PC5/6 during mouse development: GDF11 is a likely substrate. Proc Natl Acad Sci USA 105:5750–5755

    Article  CAS  PubMed  Google Scholar 

  • Farooq M, Sulochana KN, Pan X, To J, Sheng D, Gong Z, Ge R (2008) Histone deacetylase 3 (hdac3) is specifically required for liver development in zebrafish. Dev Biol 317:336–353

    Article  CAS  PubMed  Google Scholar 

  • Funkenstein B, Olekh E, Jakowlew SB (2010) Identification of a novel transforming growth factor-β (TGF-β6) gene in fish: regulation in skeletal muscle by nutritional state. BMC Mol Biol 11:37

    Google Scholar 

  • Gamer LW, Wolfman NM, Celeste AJ, Hattersley G, Hewick R, Rosen V (1999) A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a potent mesoderm inducer in Xenopus embryos. Dev Biol 208:222–232

    Article  CAS  PubMed  Google Scholar 

  • Gamer LW, Cox KA, Small C, Rosen V (2001) Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb. Dev Biol 229:407–420

    Article  CAS  PubMed  Google Scholar 

  • Ge G, Hopkins DR, Ho WB, Greenspan DS (2005) GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth-factor induced differentiation of PC12 cells. Mol Cell Biol 25:5846–5858

    Article  CAS  PubMed  Google Scholar 

  • Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98

    CAS  Google Scholar 

  • Harmon EB, Apelqvist AA, Smart NG, Gu X, Osborne DH, Kim SK (2004) GDF11 modulates NGN+ islet progenitor cell number and promotes β-cell differentiation in pancreas development. Development 131:6163–6174

    Article  CAS  PubMed  Google Scholar 

  • Holland LZ, Albalat R, Azumi K, Benito-Gutiérrez È, Blow MJ, Bronner-Fraser M et al (2008) The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Res 18:1100–1111

    Article  CAS  PubMed  Google Scholar 

  • Hubbard TJP, Aken BL, Ayling S, Ballester B, Beal K, Bragin E et al (2009) Ensembl 2009. Nucleic Acids Res 37:D690–D697

    Article  CAS  PubMed  Google Scholar 

  • Kamaci HO, Saka S, Firat K (2005) The cleavage and embryonic phase of gilthead sea bream (Sparus aurata Linnaeus, 1758) eggs. J Fish Aquat Sci 22:205–209

    Google Scholar 

  • Kawauchi S, Kim J, Santos R, Wu HH, Landers AD, Calof AL (2009) Foxg1 promotes olfactory neurogenesis by antagonizing GDF11. Development 136:1453–1464

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Wu HH, Lander AD, Lyons KM, Matzuk MM, Calof AL (2005) GDF11 controls the timing of progenitor cell competence in developing retina. Science 308:1927–1930

    Article  CAS  PubMed  Google Scholar 

  • Lee SJ, McPherron AC (1999) Myostatin and the control of skeletal muscle mass. Curr Opin Genet Dev 9:604–607

    Article  CAS  PubMed  Google Scholar 

  • Liu JP (2006) The function of growth/differentiation factor 11 (Gdf11) in rostrocaudal patterning of the developing spinal cord. Development 133:2865–2874

    Article  CAS  PubMed  Google Scholar 

  • Liu JP, Laufer E, Jessell TM (2001) Assigning the positional identity of spinal motor neurons: rostrocaudal patterning of Hox-c expression by FGFs, Gdf11, and retinoids. Neuron 32:997–1012

    Article  CAS  PubMed  Google Scholar 

  • McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member. Nature 387:83–90

    Article  CAS  PubMed  Google Scholar 

  • McPherron AC, Lawler AM, Lee SJ (1999) Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. Nat Genet 22:260–264

    Article  CAS  PubMed  Google Scholar 

  • Meyer A, Schartl M (1999) Gene and genome duplications in vertebrates: the one-to-four (-to-eight in fish) rule and the evolution of novel gene functions. Curr Opin Cell Biol 11:699–704

    Article  CAS  PubMed  Google Scholar 

  • Nakashima M, Toyono T, Akamine A, Joyner A (1999) Expression of growth/differentiation factor 11, a new member of the BMP/TGFβ superfamily during mouse embryogenesis. Mech Dev 80:185–189

    Article  CAS  PubMed  Google Scholar 

  • Nakashima M, Mizunuma K, Murakami T, Akamine A (2002) Induction of dental pulp stem cell differentiation into odontoblasts by electroporation-mediated gene delivery of growth/differentiation factor 11 (GDF11). Gene Ther 9:814–818

    Article  CAS  PubMed  Google Scholar 

  • Putnam NH, Butts T, Ferrier DE, Furlong RF, Hellsten U, Kawashima T, Robinson-Rechavi M et al (2008) The amphioxus genome and the evolution of the chordate karyotype. Nature 453:1064–1071

    Article  CAS  PubMed  Google Scholar 

  • Taylor WE, Bhasin S, Artaza J, Byhower F, Azam M, Willard DH Jr, Kull FC Jr, Gonzalez-Cadavid N (2001) Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cells. Am J Physiol Endocrinol Metab 280:E221–E228

    CAS  PubMed  Google Scholar 

  • Thomas M, Langley B, Berry C, Sharma M, Kirk S, Bass J, Kambadur R (2000) Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J Biol Chem 275:40235–40243

    Article  CAS  PubMed  Google Scholar 

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The Clustal X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882

    Article  CAS  PubMed  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  CAS  PubMed  Google Scholar 

  • Wu HH, Ivkovic S, Murray RC, Jaramillo S, Lyons KM, Johnson JE, Calof AL (2003) Autoregulation of neurogenesis by GDF11. Neuron 37:197–207

    Article  CAS  PubMed  Google Scholar 

  • Xing F, Tan X, Zhang PJ, Ma J, Zhang Y, Xu P, Xu Y (2007) Characterization of amphioxus GDF8/GDF11 gene, an archetype of vertebrate MSTN and GDF11. Dev Genes Evol 217:549–554

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We wish to thank the staff at The National Center of Mariculture, Eilat, The Salt Company, Atlit, Kibbutz Ma’agan Michael, and Mevo’ot-Yam School, Michmoret, for fish samples. We are also grateful to E. Re’em for his help with the statistical analysis. This work was supported in part by a grant from the United States–Israel Binational Agricultural Research and Development (BARD, Project No. IS-3703-05).

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Authors and Affiliations

  1. National Institute of Oceanography, Israel Oceanographic and Limnological Research, Tel Shikmona, P.O. Box 8030, Haifa, 31080, Israel

    Bruria Funkenstein & Elena Olekh

Authors
  1. Bruria Funkenstein
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  2. Elena Olekh
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Correspondence to Bruria Funkenstein.

Additional information

Communicated by M. Hammerschmidt

Electronic supplementary material

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SuppMatFig. 1

(DOC 40 kb)

SuppMatFig. 2

(DOC 35 kb)

SuppMatFig. 3

(DOC 33 kb)

SuppMatTable 1

Primers used for cloning and for gene expression (DOC 43 kb)

SuppMatTable 2

List of growth factors, species common names, abbreviations, species scientific names, and Genbank accession numbers used in alignments, phylogenetic, and syntenic analyses (DOC 33 kb)

SuppMatTable 3

Pairwise alignments of S. aurata GDF-11 precursor with fish GDF-11 (DOC 24 kb)

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Funkenstein, B., Olekh, E. Growth/differentiation factor-11: an evolutionary conserved growth factor in vertebrates. Dev Genes Evol 220, 129–137 (2010). https://doi.org/10.1007/s00427-010-0334-4

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  • DOI: https://doi.org/10.1007/s00427-010-0334-4

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