Runx3 Is Required for Hematopoietic Development in Zebrafish

Abstract

We cloned zebrafish runx3/aml2/cbfa3 and examined its expression and function during embryogenesis. In the developing embryo, runx3 is dynamically expressed in hematopoietic, neuronal, and cartilaginous tissues. Hematopoietic expression of runx3 commences late in embryogenesis in the ventral tail intermediate cell mass and later colocalizes with spi1 and lyz in circulating blood cells. In the cloche mutant, hematopoietic expression was absent, suggesting that Runx3 functions downstream of cloche in a hematopoietic pathway. Neuronal tissues expressing runx3 include the trigeminal ganglia and Rohon-Beard neurons. Runx3 appears to contribute to normal development of primitive and definitive hematopoietic cells. When Runx3 function was compromised using morpholino oligonucleotides, a reduction in the number of mature blood cells was observed. Furthermore, Runx3 depletion decreased runx1 expression in the ventral wall of the dorsal aorta and reduced the number of spi1- and lyz-containing blood cells. Conversely, ubiquitous overexpression of runx3 led to an increase in primitive blood cell numbers, together with an increase in runx1-expressing cells in the ventral wall of the dorsal aorta. We propose a role for Runx3 in the regulation of blood cell numbers. © 2003 Wiley-Liss, Inc.