Genetic control of segmentation in the vertebrate hindbrain.

Studies of cell commitment and gene expression suggest that the subdivision of the hindbrain into segments and the specification of their anteroposterior identity emerges from a prepattern in the early neural plate. This prepattern imposes a regional specification, but not a commitment of individual cells to specific segments, and may involve the spatial expression of the Krox-20 and Hox genes. The generation of null mutants has shown that the Krox-20 gene is required for the formation of definitive r3 and r5, and the Hoxa-1 gene is required for r4 and r5 development. A mouse mutant, kreisler, has disrupted hindbrain segmentation, with r5 and r6 failing to form. Studies of gene expression in these mutants suggest that the kreisler gene has an early role, whereas the Krox-20 and Hoxa-1 genes have later roles in the formation of definitive segments. I propose that a community effect of cell-cell signaling may underlie the commitment of cells to specific segments and discuss the implications of this for the phenotype of segmentation mutants. The receptor tyrosine kinases encoded by the Sek-1, Sek-2, Sek-3, and Sek-4 genes are segmentally expressed and could mediate cell-cell interactions that regulate cell commitment and hindbrain segmentation.