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During vertebrate embryogenesis, the formation of reiterated structures along the body axis is dependent upon the generation of the somite by segmentation of the presomitic mesoderm (PSM). Notch signaling plays a crucial role in both the generation and regulation of the molecular clock that provides the spatial information for PSM cells to form somites. In a screen for novel genes involved in somitogenesis, we identified a gene encoding a Wnt antagonist, Nkd1, which is transcribed in an oscillatory manner, and may represent a new member of the molecular clock constituents. The transcription of nkd1 is extremely downregulated in the PSM of vestigial tail (vt/vt), a hypomorphic mutant of Wnt3a, whereas nkd1 oscillations have a similar phase to lunatic fringe (L-fng) transcription and they are arrested in Hes7 (a negative regulator of Notch signaling) deficient embryos. These results suggest that the transcription of nkd1 requires Wnt3a, and that its oscillation patterns depend upon the function of Hes7. Wnt signaling has been postulated to be upstream of Notch signaling but we demonstrate in this study that a Wnt-signal-related gene may also be regulated by Notch signaling. Collectively, our data suggest that the reciprocal interaction of Notch and Wnt signals, and of their respective negative feedback loops, function to organize the segmentation clock required for somitogenesis. [Copyright &y& Elsevier]

The metameric structure of the vertebrate trunk is generated by repeated formation of somites from the unsegmented presomitic mesoderm (PSM). We report the initial characterization of nine different mutants affecting segmentation that were isolated in a large-scale mutagenesis screen in Medaka (Oryzias latipes). Four mutants were identified that show a complete or partial absence of somites or somite boundaries. In addition, five mutations were found that cause fused somites or somites with irregular sizes and shapes. In situ hybridization analysis using specific markers involved in the segmentation clock and antero-posterior (A-P) polarity of somites revealed that the nine mutants can be compiled into two groups. In group 1, mutants exhibit defects in tailbud formation and PSM prepatterning, whereas A-P identity in the somites is defective in group 2 mutants. Three mutants (planlos, pll; schnelles ende, sne; samidare, sam) have characteristic phenotypes that are similar to those in zebrafish mutants affected in the Delta/Notch signaling pathway. The majority of mutants, however, exhibit somitic phenotypes distinct from those found in zebrafish, such as individually fused somites and irregular somite sizes. Thus, these Medaka mutants can be expected to provide clues to uncovering novel components essential for somitogenesis. [Copyright &y& Elsevier]