Notch signaling mediates cell fate decisions during gastrulation in Xenopus laevis

Gastrulation is one of the most critical processes in early development, leading to the formation of the three primary germ layers, the ectoderm, mesoderm, and endoderm. As development proceeds, these germ layers become further specified, and will eventually give rise to all of the tissues and organs needed by an adult organism. The Notch signaling pathway is a highly conserved cell signaling pathway known to regulate a variety of developmental events. In order to investigate a possible role for Notch signaling during boundary formation between the mesoderm and endoderm during gastrulation, we manipulated Notch signaling in gastrula stage embryos and examined gene expression in resultant tissues and organs. Our findings demonstrated that the up-regulation of Notch signaling resulted in a decrease in molecular markers of the mesoderm and increased expression of endoderm markers. When Notch signaling was down-regulated, the opposite phenotype was observed. In order to extend these findings, we further sought to characterize the specific role of Notch signaling during the formation of one mesodermal derivative, the heart. While previous studies have identified a role for Notch signaling during the later stages of cardiac differentiation and morphogenesis, a role for this pathway during the earlier stages of heart field specification remained poorly defined. We provide evidence that the functional role of Notch signaling during cardiac field specification is to delay the differentiation of cardiac precursors. Furthermore, we identify a target of Notch signaling, the HES family member Esr9, as the downstream effector of Notch signaling in this and other mesodermal tissues. Finally, we begin to explore and suggest that the cardiac transcription factor GATA4 is the target of Notch signaling and Esr9 in the Notch mediated regulation of heart field formation. These findings are the first to identify and further characterize a role for Notch signaling during the earliest stages of cardiac development.