Regulation of a Vascular Plexus by <em>gata4</em> Is Mediated in Zebrafish through the Chemokine <em>sdf1a</em>

<div><p>Using the zebrafish model we describe a previously unrecognized requirement for the transcription factor <em>gata4</em> controlling embryonic angiogenesis. The development of a vascular plexus in the embryonic tail, the caudal hematopoietic tissue (CHT), fails in embryos depleted of <em>gata4</em>. Rather than forming a normal vascular plexus, the CHT of <em>gata4</em> morphants remains fused, and cells in the CHT express high levels of osteogenic markers <em>ssp1</em> and <em>runx1</em>. Definitive progenitors emerge from the hemogenic aortic endothelium, but fail to colonize the poorly vascularized CHT. We also found abnormal patterns and levels for the chemokine <em>sdf1a</em> in <em>gata4</em> morphants, which was found to be functionally relevant, since the embryos also show defects in development of the lateral line, a mechano-sensory organ system highly dependent on a gradient of <em>sdf1a</em> levels. Reduction of <em>sdf1a</em> levels was sufficient to rescue lateral line development, circulation, and CHT morphology. The result was surprising since neither <em>gata4</em> nor <em>sdf1a</em> is obviously expressed in the CHT. Therefore, we generated transgenic fish that conditionally express a dominant-negative <em>gata4</em> isoform, and determined that <em>gata4</em> function is required during gastrulation, when it is co-expressed with <em>sdf1a</em> in lateral mesoderm. Our study shows that the <em>gata4</em> gene regulates <em>sdf1a</em> levels during early embryogenesis, which impacts embryonic patterning and subsequently the development of the caudal vascular plexus.</p>