Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis

Notch signaling mediates numerous developmental cell fate decisions in orga nisms ranging from flies to humans, resulting in the generation of multiple cell types from equipotential precursors. In this paper, we present eviden ce that activation of Notch by its ligand Serrate apportions myogenic and n on-myogenic cell fates within the early Xenopus heart field. The crescent-s haped field of heart mesoderm is specified initially as cardiomyogenic, Whi le the ventral region of the field forms the myocardial tube, the dorsolate ral portions lose myogenic potency and form the dorsal mesocardium and peri cardial roof (Raffin, M., Leong, L. M., Rones, M. S., Sparrow, D., Mohun, T . and Mercola, M. (2000) Dev. Biol., 218, 326-340), The local interactions that establish or maintain the distinct myocardial and non-myocardial domai ns have never been described. Here we show that Xenopus Notch1 (Xotch) and Serrate1 are expressed in overlapping patterns in the early heart field. Co nditional activation or inhibition of the Notch pathway with inducible domi nant negative or active forms of the RBP-J/Suppressor of Hairless [Su(H)] t ranscription factor indicated that activation of Notch feeds back on Serrat e1 gene expression to localize transcripts more dorsolaterally than those o f Notch1, with overlap in the region of the developing mesocardium, Moreove r, Notch pathway activation decreased myocardial gene expression and increa sed expression of a marker of the mesocardium and pericardial roof, whereas inhibition of Notch signaling had the opposite effect. Activation or inhib ition of Notch also regulated contribution of individual cells to the myoca rdium. Importantly, expression of Nkx2.5 and Gata4 remained largely unaffec ted, indicating that Notch signaling functions downstream of heart field sp ecification. We conclude that Notch signaling through Su(H) suppresses card iomyogenesis and that this activity is essential for the correct specificat ion of myocardial and non-myocardial cell fates.