Pitx2 regulates cardiac left–right asymmetry by patterning second cardiac lineage-derived myocardium

Developmental Biology

Chenleng Cai¹  Di Ai²  James F. Martin²  Sylvia Evans¹  Brian L. Black³  Mei-Fang Lu²  Lijiang Ma²  Nigel A. Brown⁴  Wei Liu²  Michael P. Verzi³  Philip J. Gage⁵  Feiyan Dong²  Degang Wang² 

[1] Institute of Molecular Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA;Institute of Biosciences and Technology, Texas A and M System, Health Science Center, 2121 Holcombe Blvd, Houston, TX 77030, USA;Cardiovascular Research Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2240, USA;Division of Basic Medical Sciences, St. George’s Hospital Medical School, University of London, Cranmer Terrace, London SW17 ORE, UK;Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48109, USA

DOI  :  10.1016/j.ydbio.2006.06.009

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Currentmodelsofleftndash;rightasymmetryholdthatanearlyasymmetricsignalisgeneratedatthenodeandtransducedtolateralplatemesoderminalinearsignaltransductioncascadethroughthefunctionoftheNodalsignalingmolecule.ThePitx2homeoboxgenefunctionsatthefinalstagesofthiscascadetodirectasymmetricmorphogenesisofselectedorgansincludingtheheart.WepreviouslyshowedthatPitx2regulatedanasymmetricpathwaythatwasindependentofcardiacloopingsuggestingasecondasymmetriccardiacpathway.IthasbeenproposedthatinthecardiacoutflowtractPitx2functionsinbothcardiacneuralcrest,asatargetofcanonicalWnt-signaling,andinthemesoderm-derivedcardiacsecondlineage.Weusedfatemapping,conditionallossoffunction,andchimeraanalysisinmicetoinvestigatetheroleofPitx2inoutflowtractmorphogenesis.OurfindingsrevealthatPitx2isdispensableinthecardiacneuralcrestbutfunctionsinsecondlineagemyocardiumrevealingthatthiscardiacprogenitorfieldispatternedasymmetrically.

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