The mesp family of transcription factors is known to be involved in somite, cardiovascular, and haematopoietic development in various experimental systems. However, it is unclear if their role in cardiogenesis is universal, and if they are master regulators that affect the specification and/or migration of cardiac progenitors. Morpholino-mediated knockdowns of zebrafish mesp genes recapitulate previously reported somitic phenotypes and reveal previously uncharacterised cardiac defects in early zebrafish development. In particular, the knockdown of zebrafish mespaa confirms its evolutionarily conserved function in early cardiovascular and blood development. To understand the mechanisms by which the Mespaa transcription factor exerts its function, we utilise an integrated genomics approach to identify direct Mespaa transcriptional targets that may be affected in its loss-of-function phenotype.