Differential contributions of Mesp1 and Mesp2 to the epithelialization and rostro-caudal patterning of somites

Mesp1 and Mesp2 are homologous basic helix-loop-helix (bHLH) transcription factors that are co-expressed in the anterior presomitic mesoderm (PSM) just prior to somite formation. Analysis of possible functional redundancy of Mesp1 and Mesp2 has been prevented by the early developmental arrest of Mesp1/Mesp2 double-null embryos. Here we performed chimera analysis, using either Mesp2-null cells or Mesp1/Mesp2 double-null cells, to clarify (1) possible functional redundancy and the relative contributions of both Mesp1 and Mesp2 to somitogenesis and (2) the level of cell autonomy of Mesp functions for several aspects of somitogenesis. Both Mesp2-null and Mesp1/Mesp2 double-null cells failed to form initial segment borders or to acquire rostral properties, confirming that the contribution of Mesp1 is minor during these events. By contrast, Mesp1/Mesp2 double-null cells contributed to neither epithelial somite nor dermomyotome formation, whereas Mesp2-null cells partially contributed to incomplete somites and the dermomyotome. This indicates that Mesp1 has a significant role in the epithelialization of somitic mesoderm. We found that the roles of the Mesp genes in epithelialization and in the establishment of rostral properties are cell autonomous. However, we also show that epithelial somite formation, with normal rostro-caudal patterning, by wild-type cells was severely disrupted by the presence of Mesp mutant cells, demonstrating non-cell autonomous effects and supporting our previous hypothesis that Mesp2 is responsible for the rostro-caudal patterning process itself in the anterior PSM, via cellular interaction.