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Sökning: WFRF:(Schroth M.) > (2015-2019) > Cloche is a bHLH-PA...

  • Reischauer, SvenUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany. (författare)

Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification

  • Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

  • 2016-07-13
  • Springer Science and Business Media LLC,2016
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:su-132941
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-132941URI
  • https://doi.org/10.1038/nature18614DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:133913505URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-300451URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells(1-4) and a significant increase in cardiomyocyte numbers(5). Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation(1-7) and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location. Here we used a deletion allele of cloche to identify several new cloche candidate genes within this genomic region, and systematically genome-edited each candidate. Through this comprehensive interrogation, we succeeded in isolating the cloche gene and discovered that it encodes a PAS-domain-containing bHLH transcription factor, and that it is expressed in a highly specific spatiotemporal pattern starting during late gastrulation. Gain-of-function experiments show that it can potently induce endothelial gene expression. Epistasis experiments reveal that it functions upstream of etv2 and tal1, the earliest expressed endothelial and haematopoietic transcription factor genes identified to date. A mammalian cloche orthologue can also rescue blood vessel formation in zebrafish cloche mutants, indicating a highly conserved role in vertebrate vasculogenesis and haematopoiesis. The identification of this master regulator of endothelial and haematopoietic fate enhances our understanding of early mesoderm diversification and may lead to improved protocols for the generation of endothelial and haematopoietic cells in vivo and in vitro.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Stone, Oliver A.Karolinska Institutet,Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany. (författare)
  • Villasenor, AlethiaUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany. (författare)
  • Chi, NeilUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Univ Calif San Diego, Inst Genom Med, Div Cardiol, Dept Med, La Jolla, CA 92037 USA. (författare)
  • Jin, Suk-WonUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Gwangju Inst Sci & Technol, Sch Life Sci, Gwangju 61005, South Korea.;Yale Univ, Sch Med, Yale Cardiovasc Res Ctr, New Haven, CT 06511 USA. (författare)
  • Martin, MarcelStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-17121 Solna, Sweden.,Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany.(Swepub:su)marcm (författare)
  • Lee, Miler T.Yale Univ, Dept Genet, Sch Med, New Haven, CT 06520 USA.;Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. (författare)
  • Fukuda, NanaMax Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany. (författare)
  • Marass, MicheleMax Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany. (författare)
  • Witty, AlecUniv Calif San Diego, Inst Genom Med, Div Cardiol, Dept Med, La Jolla, CA 92037 USA. (författare)
  • Fiddes, IanUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Univ Calif Santa Cruz, Genom Inst, Santa Cruz, CA 95064 USA.;Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. (författare)
  • Kuo, TaiyiUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA.;Columbia Univ Coll Phys & Surg, Berrie Diabet Ctr, 630 W 168th St, New York, NY 10032 USA. (författare)
  • Chung, Won-SukUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon 34141, South Korea. (författare)
  • Salek, SherveenUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21224 USA. (författare)
  • Lerrigo, RobertUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Univ Washington, Div Gen Internal Med, Seattle, WA 98104 USA. (författare)
  • Alsio, JessicaUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Novartis, CH-4056 Basel, Switzerland. (författare)
  • Luo, ShujunIllumina, San Diego, CA 92122 USA.;Personalis, Menlo Pk, CA 94025 USA. (författare)
  • Tworus, DominikaKarolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. (författare)
  • Augustine, Sruthy M. (författare)
  • Mucenieks, SophieMax Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany. (författare)
  • Nystedt, BjörnUppsala universitet,Molekylär evolution(Swepub:uu)bjsal623 (författare)
  • Giraldez, Antonio J.Yale Univ, Dept Genet, Sch Med, New Haven, CT 06520 USA. (författare)
  • Schroth, Gary P.Illumina, San Diego, CA 92122 USA. (författare)
  • Andersson, OlovKarolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. (författare)
  • Stainier, Didier Y. R.Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany. (författare)
  • Karolinska InstitutetUniv Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.;Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Nature: Springer Science and Business Media LLC535:7611, s. 294-2980028-08361476-4687

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