Early lineage restriction in temporally distinct populations of Mespl progenitors during mammalian heart development

Cardiac development arises from two sources of mesoderm progenitors, the first heart field (FHF) and the second (SHF). Mespl has been proposed to mark the most primitive multipotent cardiac progenitors common for both heart fields. Here, using clonal analysis of the earliest prospective cardiovascular progenitors in a temporally controlled manner during early gastrulation, we found that Mespl progenitors consist of two temporally distinct pools of progenitors restricted to either the FHF or the SHE FHF progenitors were unipotent, whereas SHF progenitors were either unipotent or bipotent. Microarray and single-cell PCR with reverse transcription analysis of Mespl progenitors revealed the existence of molecularly distinct populations of Mespl progenitors, consistent with their lineage and regional contribution. Together, these results provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors that independently express Mespl at different time points during their specification, revealing that the regional segregation and lineage restriction of cardiac progenitors occur very early during gastrulation.