GENETIC-CONTROL OF SEGMENTATION IN THE VERTEBRATE HINDBRAIN

Studies of cell commitment and gene expression suggest that the subdiv ision of the hindbrain into segments and the specification of their an teroposterior identity emerges from a prepattern in the early neural p late. This prepattern imposes a regional specification, but not a comm itment of individual cells to specific segments, and may involve the s patial 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 r 5 development. A mouse mutant, kreisler, has disrupted hindbrain segme ntation, with r5 and r6 failing to form. Studies of gene expression in these mutants suggest that the kreisler gene has an early role, where as the Krox-20 and Hoxa-1 genes have later roles in the formation of d efinitive segments. I propose that a community effect of cell-cell sig naling may underlie the commitment of cells to specific segments and d iscuss the implications of this for the phenotype of segmentation muta nts. 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 .