DISRUPTION OF KROX-20 RESULTS IN ALTERATION OF RHOMBOMERE-3 AND RHOMBOMERE-5 IN THE DEVELOPING HINDBRAIN

The zinc finger gene Krox-20 is transcribed in two alternate segments (rhombomeres) of the developing hindbrain. To investigate its function , we have used homologous recombination to generate mice carrying an i n-frame insertion of the E. coli lacZ gene within Krox-20. Analysis of the beta-galactosidase pattern in heterozygous embryos confirmed the known profile with expression restricted to rhombomeres (r) 3 and 5. M ice homozygous for the mutation die during the first two weeks after b irth. Anatomical analysis of the hindbrain and of the cranial nerves d uring embryogenesis, combined with the determination of the expression patterns of rhombomere-specific genes, demonstrated that Krox-20 inac tivation results in a marked reduction or elimination of r3 and r5. We conclude that Krox-20, although not required for the initial delimita tion of r3 and r5, plays an important role in the process of segmentat ion governing hindbrain development.