Analysis of hindbrain patterning defects caused by the kreislerenu mutation reveals multiple roles of Kreisler in hindbrain segmentation

The embryonic hindbrain is subdivided into eight subunits, termed rhombomeres (r1–r8). The Kreisler (Krml1/MafB/val) transcription factor is expressed in and essential for patterning rhombomeres 5 and 6. Here, we have shown that in the chemically induced kreislerenu (krenu) allele, a point mutation in the DNA binding domain abolishes or severely reduces Kreisler‐dependent transcription. Comparison of krenu/krenu embryos with those homozygous for the classic kreisler (kr) mutation has reconciled past discrepancies and revealed multiple roles of Kreisler in hindbrain segmentation. These analyses demonstrate that Kreisler is required for maintenance and expansion but not initiation of the Krox20 expressing r5 domain. The differences in the “r5‐like” phenotype of krenu/krenu and kr/kr mouse embryos, and zebrafish carrying mutations in the Kreisler orthologue valentino (val) suggest that Kreisler performs many of its r5‐specific functions by associating with other proteins. By contrast, kr/kr and krenu/krenu mouse and val‐/‐ zebrafish embryos all exhibit indistinguishable defects in r6 specification. Thus, transcriptionally active Kreisler is required for r6 specification. Unlike mouse krenu/krenu and zebrafish val‐/‐ embryos, kr/kr embryos exhibited anterior defects. We determined that the kr chromosomal inversion caused ectopic Kreisler expression in r3 of kr/kr and kr/+ embryos. Hence, Kreisler regulates maintenance and expansion of r5 and specification of r6 but is not required for r3 development. Developmental Dynamics 227:134–142, 2003. © 2003 Wiley‐Liss, Inc.

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