osr1couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation

Transcriptional regulatory networks refine gene expression boundaries throughout embryonic development to define the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and its neighboring vessel progenitors are poorly understood. Here, we delineate new roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafishosr1mutants display decreased IM formation and premature emergence of neighboring lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss ofhand2partially suppresses theosr1mutant phenotypes.hand2andosr1are both expressed in the posterior lateral mesoderm, butosr1expression decreases dramatically prior to LVP emergence. Overexpressingosr1inhibits LVP development while enhancing IM formation. Together, our data demonstrate thatosr1modulates both the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels ofosr1andhand2expression is essential to demarcate the dimensions of kidney and vessel progenitor territories.SUMMARY STATEMENTAnalysis of theosr1mutant phenotype reveals roles in determining the extent of intermediate mesoderm formation while inhibiting premature differentiation of neighboring vessel progenitors.