Molecular regulation of anterior and posterior cell fates in the primitive streak stage avian embryo

Understanding the molecular signals involved in cell lineage decisions is becoming increasingly important for clinical applications. Recruitment of multipotential embryonic stem cells to the cardiomyogenic lineage is being pursued to repair cardiovascular injury in vivo. The current studies were aimed at unraveling the molecular pathways active in the lateral plate mesoderm that establish the cardiac cell fate in the anterior of primitive streak stage chicken embryos. Experiments were focused on the chicken model system because of the ease of accessibility and experimental manipulation during early development. Initially, explantation studies were undertaken to clarify inconsistencies among classical fate maps of the cardiac progenitors in the gastrulating avian embryo and to reconcile this position with the expression of genes implicated in early cardiogenesis. Previous evidence indicates the existence of a positive cardiac inductive pathway in the anterior regulated by Bone Morphogenetic Proteins (BMPs) that activates the expression of the earliest known cardiac marker, cNkx-2.5. Coincidence of the expression of these genes with the redefined lateral position of the cardiac progenitors in the anterior mesoderm indicates for the first time that prospective heart cells are in contact with a positive cardiac inductive signal as soon as they migrate to the lateral plate. Additionally, expression of the activin type IIa receptor in regions responsive to BMP-2 suggests a role in the BMP-2/cNkx-2.5 cardiac inductive pathway. Further experiments indicate that cardiogenic cell fates are negatively regulated in the posterior lateral plate mesoderm by a pathway activated by the caudal-related transcription factor, cCdx-B. cCdx-B is expressed throughout the posterior non-cardiogenic region in the gastrulating avian embryo, and activates the expression of posterior Hox genes and the Wnt signaling family member, cWnt-8c. Recent evidence indicates that cWnt-8c, a promoter of non-cardiogenic cell fates, also inhibits cardiogenesis in the posterior mesoderm. These results suggest that activation of a non-cardiogenic lineage pathway by cCdx-B also negatively regulates cardiogenesis in the posterior lateral plate mesoderm. Taken together, these studies have extended the knowledge of the complex molecular pathways involved in lineage decisions in the lateral plate mesoderm that limit cardiogenesis to anterior lateral cells during early embryonic development.