Gata5 is required for the development of the heart and endoderm in zebrafish

Abstract

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.

Different requirements for GATA factors in cardiogenesis are mediated by non‐canonical Wnt signaling

“…Knockout and overexpression experiments have revealed important roles for GATA5 during Zebrafish cardiogenesis (Reiter et al, 1999), but not in mouse as suggested by the GATA5 mutant mice (Molkentin et al, 2000). Furthermore, initial analysis of GATA5 function in Xenopus using a translation-blocking MO (tlMO) had suggested no role in cardiogenesis (Peterkin et al, 2007), which, however, was called into question in a recent study that used a newly designed splice-blocking MO (spMO) (Haworth et al, 2008) to suggest an important role for Xenopus GATA5 during early embryogenesis.…”

“…In contrast to zebrafish where a critical role for GATA5 in specification of the myocardium was demonstrated (Reiter et al, 1999), gene knockout studies in mice suggested that GATA5 was dispensable for embryonic development (Molkentin et al, 2000). These mouse findings seemed to be supported by initial Xenopus studies reporting only a minor role for GATA5 in heart formation (Peterkin et al, 2007).…”

“…GATA proteins are transcription factors, which regulate diverse processes during embryogenesis and in adults (Patient and McGhee, 2002). The GATA4, 5, and 6 genes are all important in vertebrates for endoderm formation (Weber et al, 2000;Afouda et al, 2005) and are central regulators of heart development (Gove et al, 1997;Reiter et al, 1999;Peterkin et al, 2003Peterkin et al, , 2007Holtzinger and Evans, 2005;Afouda et al, 2008;Haworth et al, 2008;Takeuchi and Bruneau, 2009). They have overlapping spatial and temporal expression patterns and regulate cardiomyogenesis in a partially redundant manner (Holtzinger and Evans, 2007;Peterkin et al, 2007).…”

Cardiac patterning and morphogenesis in zebrafish

“…In zebrafish, most, but not all, of the nkx2.5-expressing cells terminally differentiate into myocardiocytes (Serbedzija et al, 1998;. Differentiating myocardiocytes initiate expression of genes that encode cardiac sarcomere proteins, such as cmlc1 and cmlc2 (Reiter et al, 1999;Yelon et al, 1999) (Fig. 2).…”

“…The transcription factor gene gata5 is expressed in a broad region of the ALPM, including the portion that expresses nkx2.5 (Reiter et al, 1999). Mutation of the faust/gata5 locus results in a dramatic reduction of nkx2.5 expression (Reiter et al, 1999).…”