The winged helix transcription factor Foxc1a is essential for somitogenesis in zebrafish

Previous studies identified zebrafish foxc1a and foxc1b as homologs of the mouse forkhead gene, Foxc1. Both genes are transcribed in the unsegmented p resomitic mesoderm (PSM), newly formed somites, adaxial cells, and head mes oderm. Here, we show that inhibiting synthesis of Foxc1a (but not Foxc1b) p rotein with two different morpholino antisense oligonucleotides blocks form ation of morphological somites, segment boundaries, and segmented expressio n of genes normally transcribed in anterior and posterior somites and expre ssion of paraxis implicated in somite epithelialization. Patterning of the anterior PSM is also affected, as judged by the absence of mesp-b, ephrinB2 , and ephA4 expression, and the down-regulation of notch5 and notch6. In co ntrast, the expression of other genes, including mesp-a and papc, in the an terior of somite primordia, and the oscillating expression of deltaC and de ltaD in the PSM appear normal. Nevertheless, this expression is apparently insufficient for the maturation of the presumptive somites to proceed to th e stage when boundary formation occurs or for the maintenance of anterior/p osterior patterning. Mouse embryos that are compound null mutants for Foxc1 and the closely related Foxc2 have no morphological somites and show abnor mal expression of Notch signaling pathway genes in the anterior PSM. Theref ore, zebrafish foxc1a plays an essential and conserved role in somite forma tion, regulating both the expression of paraxis and the A/P patterning of s omite primordia.