Patterning of the Primitive Heart Tube in Zebrafish

Summary

Principal Investigator: Jau Nian Chen
Abstract: Abnormalities in the formation and/or function of the embryonic heart often lead to embryonic lethality or severe health problems later in life. Understanding the fundamental mechanisms underlying early heart development at the cellular and molecular level is not only scientifically challenging but is also clinically relevant. We choose the zebrafish as our model organism to study early cardiac patterning because it is amenable to genetic, embryological and molecular manipulation. Furthermore, the embryonic hearts of all vertebrate species undergo similar morphogenic processes and are regulated by conserved genetic circuits. Information obtained from one model organism may apply to other vertebrates, including humans. In this project, we take three independent approaches to study the cellular and molecular mechanisms governing primitive heart tube morphogenesis. Our recent study on the zebrafish heart and mind mutation uncovered an unexpected role of Na,K-ATPase a1B1 in the elongation of the primitive heart tube. We will investigate the impact of loss of function of Na,K-ATPase a1 B1 on the cellular architecture of cardiomyocytes. We will also investigate the interaction of Na,K-ATPase a1 B1 other genes critical for the morphogenesis of the primitive heart tube in zebrafish at the cellular and genetic level (Aim 1). Furthermore we will investigate the molecular mechanism by which the Na,K-ATPase a1 B1 regulates the elongation of the primitive heart tube in the zebrafish and in cultured cells, as the first step toward understanding genetic networks involved in the primitive heart tube formation (Specific Aim 2). Finally, from an ongoing zebrafish genetic screen, we identified a new mutation affecting the patterning of the primitive heart tube. We will characterize the phenotypes of this mutant and identify the molecular lesion causing this mutant phenotype (Aim 3). The combination of cellular, molecular and genetic studies proposed in this project will provide new and in-depth insight into mechanisms of primitive heart tube morphogenesis.
Funding Period: ----------------2007 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Calcium signaling: a common thread in vertebrate left-right axis development
    Adam Langenbacher
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Dev Dyn 237:3491-6. 2008
  2. pmc The PAF1 complex component Leo1 is essential for cardiac and neural crest development in zebrafish
    Catherine T Nguyen
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Dev Biol 341:167-75. 2010
  3. pmc Aplexone targets the HMG-CoA reductase pathway and differentially regulates arteriovenous angiogenesis
    Jayoung Choi
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Development 138:1173-81. 2011
  4. pmc The PAF1 complex differentially regulates cardiomyocyte specification
    Adam D Langenbacher
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Dev Biol 353:19-28. 2011
  5. pmc Mutation in utp15 disrupts vascular patterning in a p53-dependent manner in zebrafish embryos
    Kevin Mouillesseaux
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 6:e25013. 2011
  6. pmc Sodium pump activity in the yolk syncytial layer regulates zebrafish heart tube morphogenesis
    Adam D Langenbacher
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Dev Biol 362:263-70. 2012

Scientific Experts

  • Jau Nian Chen
  • Adam D Langenbacher
  • Kevin Mouillesseaux
  • Catherine T Nguyen
  • Adam Langenbacher
  • Jie Huang
  • Jayoung Choi
  • Yi Chen
  • Fei Lu
  • Sape S Kinderman
  • Zhiming Wang
  • Ohyun Kwon
  • Hannah D G Fiji
  • Georg W Otto
  • Robert Geisler
  • Ann M Cavanaugh
  • Michael Hsieh

Detail Information

Publications7

  1. pmc Calcium signaling: a common thread in vertebrate left-right axis development
    Adam Langenbacher
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Dev Dyn 237:3491-6. 2008
    ..This review will summarize the diverse pathways involved in the break of left-right symmetry and explore in depth the multiple roles of calcium in vertebrate left-right axis specification...
  2. pmc The PAF1 complex component Leo1 is essential for cardiac and neural crest development in zebrafish
    Catherine T Nguyen
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Dev Biol 341:167-75. 2010
    ..Taken together, these results provide the first genetic evidence of the requirement for Leo1 in the development of the heart and neural crest cell populations...
  3. pmc Aplexone targets the HMG-CoA reductase pathway and differentially regulates arteriovenous angiogenesis
    Jayoung Choi
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Development 138:1173-81. 2011
    ..Taken together, our findings indicate that angiogenesis is differentially regulated by the HMGCR pathway via an arteriovenous-dependent requirement for protein prenylation in zebrafish and human endothelial cells...
  4. pmc The PAF1 complex differentially regulates cardiomyocyte specification
    Adam D Langenbacher
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Dev Biol 353:19-28. 2011
    ..Our findings demonstrate critical but differential requirements for PAF1C components in zebrafish cardiac specification and heart morphogenesis...
  5. pmc Mutation in utp15 disrupts vascular patterning in a p53-dependent manner in zebrafish embryos
    Kevin Mouillesseaux
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 6:e25013. 2011
    ..Using the zebrafish as a model organism, we sought to identify genes that influence normal vascular patterning...
  6. pmc Sodium pump activity in the yolk syncytial layer regulates zebrafish heart tube morphogenesis
    Adam D Langenbacher
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Dev Biol 362:263-70. 2012
    ..Together, these data reveal a new non-cell autonomous role for Atp1a1 in cardiac morphogenesis and establish Na(+),K(+) ATPase as a major player in the genetic pathway by which the YSL regulates embryonic ECM deposition...