Mechanisms regulating latent cardiac potential in the anterior lateral plate mesoderm

Development of the vertebrate heart begins with the specification and differentiation of multipotent progenitors, thought to be located within a special embryonic territory termed the heart field. Within this hypothetical field, it was proposed that progenitors receive local inductive signaling that promotes cardiac fate, as well as repressive signaling to restrict field size. The end result of these opposing developmental cues is the precise, localized production of cardiomyocytes required to assemble the heart. A major hurdle to verifying heart field existence is that the location of cardiac progenitors and identity of gene products that regulate cardiac specification remain poorly defined.; My work provides evidence in support of heart field-mediated cardiac specification. Using both fate mapping and marker analysis, I identified a region within the zebrafish anterior lateral plate mesoderm (ALPM) that givesrise to cardiomyocytes. This territory of ALPM is flanked rostrally by another ALPM territory that does not normally produce cardiac lineages, but instead generates head vasculature and myeloid blood. In the absence of myeloid blood and head vessel specification, rostral ALPM undergoes respecification, resulting in the production of excess cardiomyocytes. This indicates that rostral ALPM retains cardiac potential that is normally suppressed by factors that are required for head vessel and myeloid blood specification.; With the development of stem cell-based therapies to treat congenital and degenerative cardiac diseases, knowledge of the regulative processes that promote and restrict stem cell cardiac potential will become increasingly critical. My studies, which suggest mutual exclusivity between cardiac and blood vessel/myeloid blood fate specification, could provide new means to harness stem cell potential in order to develop cell-based therapies.