Mesp2 initiates somite segmentation through the Notch signalling pathway

The Notch-signalling pathway is important in establishing metameric pattern during somitogenesis. In mice, the lack of either of two molecules involve d in the Notch-signalling pathway. Mesp2 or presenilin-1 (Ps1), results in contrasting phenotypes: caudalized versus rostralized vertebra. Here we ado pt a genetic approach to analyse the molecular mechanism underlying the est ablishment of rostro-caudal polarity in somites. By focusing on the fact th at expression of a Notch ligand, DII1, is important for prefiguring somite identity, we found that Mesp2 initiates establishment of rostro-caudal pola rity by controlling two Notch-signalling pathways. Initially, Mesp2 activat es a Ps1-independent Notch-signalling cascade to suppress DII1 expression a nd specify the rostral half of the somite. Ps1-mediated Notch-signalling is required to induce DII1 expression in the caudal half of the somite. There fore, Mesp2- and Ps1-dependent activation of Notch-signalling pathways migh t differentially regulate DII1 expression, resulting in the establishment o f the rostro-caudal polarity of somites.