The Notch-signalling pathway is important in establishing metameric pattern during somitogenesis. In mice, the lack of either of two molecules involved in the Notch-signalling pathway, Mesp2 or presenilin-1 (Ps1), results in contrasting phenotypes: caudalized versus rostralized vertebra. Here we adopt a genetic approach to analyse the molecular mechanism underlying the establishment of rostro-caudal polarity in somites. By focusing on the fact that expression of a Notch ligand, Dll1, is important for prefiguring somite identity, we found that Mesp2 initiates establishment of rostro-caudal polarity by controlling two Notch-signalling pathways. Initially, Mesp2 activates a Ps1-independent Notch-signalling cascade to suppress Dll1 expression and specify the rostral half of the somite. Ps1-mediated Notch-signalling is required to induce Dll1 expression in the caudal half of the somite. Therefore, Mesp2- and Ps1-dependent activation of Notch-signalling pathways might differentially regulate Dll1 expression, resulting in the establishment of the rostro-caudal polarity of somites.
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We thank R. Conlon (Notch1 cDNA), A. Gossler (Dll1 cDNA), P. Gruss (Uncx4.1 cDNA), R. Kageyama (Hes5 cDNA) and E.M. De Robertis (Cer1 cDNA) for providing reagents; and W. Murai, M. Ikumi, S. Sinzawa, M. Uchida and S. Takeda for technical assistance. This work was supported in part by Grants in Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture in Japan and Special Coordination Funds for Promoting Science and Technology to Y.S., and grants from the Mochida Memorial Foundation for Medical and Pharmaceutical Research, Uehara Memorial Foundation and Ichiro Kanehara Foundation to H.K.
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Takahashi, Y., Koizumi, K., Takagi, A. et al. Mesp2 initiates somite segmentation through the Notch signalling pathway . Nat Genet 25, 390–396 (2000). https://doi.org/10.1038/78062
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