Fig. 7. (A) Summary of putative signaling cascades in the anterior PSM. The Psen1-independent pathways are shown with green arrows. Dll1-Notch signaling results in induction of both Dll1 itself and Mesp2. The positive feedback of Dll1 is mediated by the Psen1-dependent signal. Induction of Mesp2 is mediated via Psen1-independent Dll1-Notch signaling and Psen1-dependent Dll3-Notch signaling. In contrast to Dll1, Dll3 has roles in upregulation of Mesp2 and suppression of Dll1 and Uncx4.1. (B) Integration of stripe pattern by Dll3 function. For simplification, anterior PSM cells of four-cell width are illustrated. Pink cells represent the dominance of the Mesp2 function, and blue cells the dominance of the Dll1 function. Genes and arrows are shown only between two representative cells for simplicity. The green arrows show the Psen1-independent pathways and broken lines show inactive states. Even in the absence of Dll3, Dll1-Notch signaling and Mesp2 are still active (left). Reciprocal Dll1-Notch signaling between two neighboring cells results in induction of Dll1 in both cells. Meanwhile, reciprocal Dll1-Notch signaling also induces expression of Mesp2, which suppresses expression of Dll1 cell-autonomously in both cells. When Dll1 is downregulated, Mesp2 is also reduced by the lack of the juxtacrine Dll1 signal. Thus, the positive and negative feedback loops of Dll1 and Mesp2 produce uneven spatial patterns of Dll1 and Mesp2, but fail to form integrated stripe patterns in the absence of Dll3. Although the precise mechanism is unknown, participation of Dll3 results in synchronization of Dll1-dominant and Mesp2-dominant cells by suppressing Dll1 expression in cooperation with Mesp2 (right). After segregation, Dll3 and Mesp2 continue to suppress Dll1 and Uncx4.1 expression in the rostral half, while Dll1 induces expression of Dll1 itself and Uncx4.1 via Psen1-dependent pathway in the caudal half. In the caudal half, induction of Mesp2 expression via Psen1-independent pathway is inactive.