Reiter, J. F. et al. Gata5 is required for the development of the heart and endoderm in zebrafish. Genes Dev. 13, 2983-2995

Department of Biochemistry and Biophysics, Programs in Human Genetics and Developmental Biology, University of California at San Francisco, San Francisco, California 94143-0448 USA.
Genes & Development (Impact Factor: 10.8). 12/1999; 13(22). DOI: 10.1101/gad.13.22.2983
Source: PubMed Central


The mechanisms regulating vertebrate heart and endoderm development have recently become the focus of intense study. Here we present evidence from both loss- and gain-of-function experiments that the zinc finger transcription factor Gata5 is an essential regulator of multiple aspects of heart and endoderm development. We demonstrate that zebrafish Gata5 is encoded by the faust locus. Analysis of faust mutants indicates that early in embryogenesis Gata5 is required for the production of normal numbers of developing myocardial precursors and the expression of normal levels of several myocardial genes including nkx2.5. Later, Gata5 is necessary for the elaboration of ventricular tissue. We further demonstrate that Gata5 is required for the migration of the cardiac primordia to the embryonic midline and for endodermal morphogenesis. Significantly, overexpression of gata5 induces the ectopic expression of several myocardial genes including nkx2.5 and can produce ectopic foci of beating myocardial tissue. Together, these results implicate zebrafish Gata5 in controlling the growth, morphogenesis, and differentiation of the heart and endoderm and indicate that Gata5 regulates the expression of the early myocardial gene nkx2.5.

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    • "Among the environment factors crucial for myocardial migration is the endoderm, a tissue adjacent to the cardiac mesoderm. Mouse and zebrafish mutants with endodermal defects display cardia bifida (David and Rosa, 2001; Narita et al., 1997; Reiter et al., 1999), and in chick embryos, disruption of the endoderm perturbs myocardial migration (Rosenquist, 1970). The endoderm has been reported to influence heart formation by secreting growth factors required for cardiac specification and differentiation (Andrée et al., 1998; Lough and Sugi, 2000; Nascone and Mercola, 1995; Schultheiss et al., 1995). "
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    ABSTRACT: Coordination between the endoderm and adjacent cardiac mesoderm is crucial for heart development. We previously showed that myocardial migration is promoted by convergent movement of the endoderm, which itself is controlled by the S1pr2/Gα13 signaling pathway, but it remains unclear how the movements of the two tissues is coordinated. Here, we image live and fixed embryos to follow these movements, revealing previously unappreciated details of strikingly complex and dynamic associations between the endoderm and myocardial precursors. We found that during segmentation the endoderm underwent three distinct phases of movement relative to the midline: rapid convergence, little convergence and slight expansion. During these periods, the myocardial cells exhibited different stage-dependent migratory modes: co-migration with the endoderm, movement from the dorsal to the ventral side of the endoderm (subduction) and migration independent of endoderm convergence. We also found that defects in S1pr2/Gα13-mediated endodermal convergence affected all three modes of myocardial cell migration, probably due to the disruption of fibronectin assembly around the myocardial cells and consequent disorganization of the myocardial epithelium. Moreover, we found that additional cell types within the anterior lateral plate mesoderm (ALPM) also underwent subduction, and that this movement likewise depended on endoderm convergence. Our study delineates for the first time the details of the intricate interplay between the endoderm and ALPM during embryogenesis, highlighting why endoderm movement is essential for heart development, and thus potential underpinnings of congenital heart disease. © 2015. Published by The Company of Biologists Ltd.
    Development 09/2015; 142(17). DOI:10.1242/dev.113944 · 6.46 Impact Factor
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    • "In chicks, GATA5 is transcribed in the cardiac crescent prior to the formation of primordial heart tubes (Laverriere et al. 1994). However, in zebra fish, a gata5 null mutation results in embryonic lethality with a similar phenotype to that observed in Gata4 null mice (Reiter et al. 1999). Gene targeting and transgene expression in mice will undoubtedly continue to improve our understanding on functions of various genes. "
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    ABSTRACT: In vertebrates, six GATA transcription factors, GATA1 through GATA6, have been identified and GATA1-3 is known to be involved in hematopoietic developments, while GATA4-6 play roles in cardiac and endoderm developments. Recently, we and others have found that GATA2 and GATA3 found in the trophectoderm plays a role in gene expression specific to this cell type, but GATA4-6 have not been well characterized in early embryonic developments. Using quantitative polymerase chain reaction (qPCR) and in situ hybridization, we examined the expression of GATA4, 5 and 6 messenger RNAs (mRNAs) in ovine conceptuses and uteri during the peri-implantation period. In ovine conceptuses, GATA4, 5 and 6 transcripts were present on days 15, 17 and 21 (day 0 = day of mating), and high GATA5 and 6 mRNAs were found on day 21, most of which were localized in the trophectoderm and endoderm. Moreover, minute and substantial GATA4 and 5 mRNAs were found in days 15 and 21 uterine endometria, respectively. Increase in GATA4-6 transcripts in day 21 uteri indicates that in addition to GATA1-3, GATA4-6 may also play a potentially novel role in the development of ovine trophectoderm, endoderm and/or uterine endometria following conceptus attachment to the uterine epithelium.
    Animal Science Journal 12/2013; 85(4). DOI:10.1111/asj.12156 · 0.96 Impact Factor
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    • "Our analysis places ela upstream of gata5, one of the earliest markers of mesendodermal cells, which fails to coalesce at the midline in ela mutants. Mutation in gata5 in faust zebrafish demonstrates that this transcription factor is required for precardiac mesoderm to migrate to the embryonic midline (Reiter et al., 1999). The myocardium lineage, which is one of the first paraxial cell populations to migrate into the anterior lateral plate mesoderm (ALPM), is very sensitive to changes in the endoderm lineage, which is specified by the Nodal pathway (Schier, 2003). "
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    ABSTRACT: We report here the discovery and characterization of a gene, ELABELA (ELA), encoding a conserved hormone of 32 amino acids. Present in human embryonic stem cells, ELA is expressed at the onset of zebrafish zygotic transcription and is ubiquitous in the naive ectodermal cells of the embryo. Using zinc-finger-nuclease-mediated gene inactivation in zebrafish, we created an allelic series of ela mutants. ela null embryos have impaired endoderm differentiation potential marked by reduced gata5 and sox17 expression. Loss of Ela causes embryos to develop with a rudimentary heart or no heart at all, surprisingly phenocopying the loss of the apelin receptor (aplnr), which we show serves as Ela's cognate G protein-coupled receptor. Our results reveal the existence of a peptide hormone, ELA, which, together with APLNR, forms an essential signaling axis for early cardiovascular development.
    Developmental Cell 12/2013; 27(6). DOI:10.1016/j.devcel.2013.11.002 · 9.71 Impact Factor
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