Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm.

Abstract

Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidney by restricting IM dimensions. The IM is expanded in zebrafish <i>hand2</i> mutants and is diminished when <i>hand2</i> is overexpressed. Within the posterior mesoderm, <i>hand2</i> is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and <i>hand2</i> promotes venous development while inhibiting IM formation at this interface. Furthermore, <i>hand2</i> and the co-expressed zinc-finger transcription factor <i>osr1</i> have functionally antagonistic influences on kidney development. Together, our data suggest that <i>hand2</i> functions in opposition to <i>osr1</i> to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM.