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 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.
Cellular & Molecular Toxicology Division, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
Y
Y
Takahashi
K
K
Koizumi
A
A
Takagi
S
S
Kitajima
T
T
Inoue
H
H
Koseki
Y
Y
Saga
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009154:Mutation; D053764:Presenilin-1; D051880:Receptors, Notch; D015398:Signal Transduction; D019170:Somites / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D008024:Ligands; D008565:Membrane Proteins; D053764:Presenilin-1; D051880:Receptors, Notch; D014157:Transcription Factors; C107407:Mesp2 protein, mouse; C508853:PSEN1 protein, human