Hypomorphic Mesp allele

Somitogenesis is a dynamic morphogenetic process required for the generation of a metameric architecture in vertebrates. The paraxial mesoderm derived from the primitive streak or tailbud is aligned on both sides of the neural tube as the presomitic mesoderm (PSM). For formation of the metameric structure, mesenchymal PSM cells have to undergo two types of segmentation. One is initial segmentation, which is the segment border formation between the epithelial somites and PSM. The other is called resegmentation where individual vertebral units are formed. The initial segmentation process is accompanied by the mesenchymal-epithelial transition of PSM cells. Mesenchymal cells change their shape by epithelialization and are separated from caudal cells, which maintain mesenchymal morphology. The segment border formation occurs at fixed intervals and continues until the supply of paraxial mesoderm ends. Once the somites are formed, somitic cells start to differentiate, depending on their position within the somites. Cells facing the surface ectoderm differentiate into the dermomyotome, which then gives rise to the dermatome and myotome. The medial cells, under the influence of the notochord, differentiate into the sclerotome. The second segmentation, called resegmentation, occurs only in the sclerotome, during which the rostral and caudal halves within somites are segregated and re-fused with the next neighboring halves to form vertebrae. This process proceeds because of a difference in the property of cells between the rostral and caudal compartments within the somite. Embryonic manipulation and gene expression analysis have revealed that the rostrocaudal (RC) polarity is established in the anterior PSM prior to initial segmentation (Tam et al., 2000). Mesp2 is a member of the bHLH family of transcription factors. Expression is observed mainly during somitogenesis in the presomitic mesoderm, although a transient expression is also observed in nascent mesodermal cells at the onset of gastrulation. The Mesp2-null mouse shows two major defects in somitogenesis: the lack of the initial segment border, and the loss of rostral properties of the somite, resulting in the formation of a caudalized vertebrae (Saga et al., 1997). Genetic analysis revealed that Mesp2 plays a critical role in the establishment of RC polarity within somite primordia by regulating Dll1 expression through the Notch signaling pathway (Takahashi et al., 2000). To date, in any segmentation 2473 Development 129, 2473-2481 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV2847