Differential requirement of Hand1 during differentiation of lateral plate mesoderm lineages in Xenopus laevis

The transcription factor hand1 is expressed in the heart, lateral plate mesoderm (LPM) and neural crest cells during development. Hand1-null mice die early in embryogenesis due to defects in the heart and placenta. This lethality has made our understanding of the range of functions for Hand1 in early development incomplete. In Xenopus, we observed that the hand1 expression pattern initially marked essentially all LPM derivatives and then correlated closely with a subset of specific LPM derivatives later in development. This led us to hypothesize that tight regulation of hand1 is required for normal development of LPM lineages. Using hand1 knockdown and overexpression models in Xenopus, development of LPM derivatives was compared. As in the mouse, we found that hand1 is required for proper heart morphogenesis. Hand1 is also required for the formation of a complex vascular plexus within embryos by maintaining early endothelial cell populations, however, hand1 over expression is not sufficient to induce endothelial cell differentiation. Furthermore, down regulation of hand1 is critical for the development of the hematopoietic lineages. These findings confirm a conserved role of hand1 in heart morphogenesis and suggest regulation of hand1 levels is critical for normal development of specific LPM lineages.