The anterior and posterior halves of individual somites adopt distinct fates during somitogenesis, which is crucial for establishing the metameric pattern of axial tissues such as the vertebral column and peripheral nerves. Genetic analyses have demonstrated that the specification of cells to an anterior or posterior fate is intimately related to the process of segmentation. Inactivation of the transcription factor Mesp2, or components of the Notch signaling pathway, led to defects in segmentation and a loss of anterior/posterior polarity. Target genes in mice that could mediate the morphological events associated with segmentation or polarity have not been identified. Studies in Xenopus and zebrafish have demonstrated that the protocadherin, papc, is expressed in an anterior-specific manner in the presumptive somites of the presomitic mesoderm and is required for normal somitogenesis. Here, we examine the role of papc in directing segmentation in the mouse. We demonstrate that papc is expressed in a dynamic pattern within the first two presumptive somites (0 and -1) at the anterior end of the presomitic mesoderm. The domain of papc transcription in somite 0 starts broad and becomes progressively restricted to the anterior edge. Transcription in somite -1 over the same time remains broad. Analysis of targeted null mutations revealed that transcription of papc is dependent on Mesp2. The dynamic nature of papc transcription in somite 0 requires the expression of lunatic fringe, which modifies the activation of the Notch signaling pathway and is required for proper segmentation of somites. Treatment of embryonic mouse tails in a hanging drop culture with a putative dominant-negative mutation of papc disrupted the epithelial organization of cells at the segmental borders between somites. Together, these data indicate that papc is an important regulator of somite epithelialization associated with segmentation.
Copyright 2003 Elsevier Science (USA)