GATA-5 - A TRANSCRIPTIONAL ACTIVATOR EXPRESSED IN A NOVEL TEMPORALLY AND SPATIALLY-RESTRICTED PATTERN DURING EMBRYONIC-DEVELOPMENT

Members of the GATA family of zinc finger transcription factors regula te critical steps of cellular differentiation during vertebrate develo pment. In the studies described in this report, we have isolated and f unctionally characterized the murine GATA-5 cDNA and protein and defin ed the temporal and spatial pattern of GATA-5 gene expression during m ammalian development. The amino terminus of the mouse GATA-5 protein s hares high level amino acid sequence identity with the murine GATA-4 a nd -6 proteins, but not with other members of the GATA family. GATA-5 binds to the functionally important CEF-1 nuclear protein binding site in the cardiac-specific slow/cardiac troponin C (cTnC) transcriptiona l enhancer and overexpression of GATA-5 transactivates the cTnC enhanc er in noncardiac muscle cell Lines. During embryonic and postnatal dev elopment, the pattern of GATA-5 gene expression differs significantly from that of other GATA family members. In the primitive streak embryo , GATA-5 mRNA is detectable in the precardiac mesoderm. Within the emb ryonic heart, the GATA-5 gene is expressed within the atrial and ventr icular chambers (ED 9.5), becomes restricted to the atrial endocardium (ED 12.5), and is subsequently not expressed in the heart during late fetal and postnatal development. Moreover, coincident with the earlie st steps in lung development, only the GATA-5 gene is expressed within the pulmonary mesenchyme. Finally, the GATA-5 gene is expressed in ti ssue-restricted subsets of smooth muscle cells (SMCs), including bronc hial SMCs and SMCs in the bladder wall. These data are consistent with a model in which GATA-5 performs a unique temporally and spatially re stricted function in the embryonic heart and lung. Moreover, these dat a suggest that GATA-5 may play an important role in the transcriptiona l program(s) that underlies smooth muscle cell diversity. (C) 1997 Aca demic Press.