title: Analysis of hindbrain patterning defects caused by the kreisler(enu) mutation reveals multiple roles of Kreisler in hindbrain segmentation.
abstract: 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 kreisler(enu) (kr(enu)) allele, a point mutation in the DNA binding domain abolishes or severely reduces Kreisler-dependent transcription. Comparison of kr(enu)/kr(enu) 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 kr(enu)/kr(enu) 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 kr(enu)/kr(enu) mouse and val-/- zebrafish embryos all exhibit indistinguishable defects in r6 specification. Thus, transcriptionally active Kreisler is required for r6 specification. Unlike mouse kr(enu)/kr(enu) 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.
authors.affiliation: Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Sadl
authors.forename: Angela
authors.initials: A
authors.lastname: Sing
authors.forename: Lynn
authors.initials: L
authors.lastname: Mar
authors.forename: Fuzi
authors.initials: F
authors.lastname: Jin
authors.forename: Sabine P
authors.initials: SP
authors.lastname: Cordes
mesh_terms: D000483:Alleles; D000818:Animals; D030161:Avian Proteins; D001665:Binding Sites; D019521:Body Patterning; D019556:COS Cells; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D017930:Genes, Reporter; D017403:In Situ Hybridization; D050977:Maf Transcription Factors; D051258:MafB Transcription Factor; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015513:Oncogene Proteins; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012249:Rhombencephalon / Q000033:anatomy & histology / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D029961:Zebrafish Proteins
chemical_list: D030161:Avian Proteins; D004268:DNA-Binding Proteins; D050977:Maf Transcription Factors; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D015513:Oncogene Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C490408:mafbb protein, zebrafish; D004247:DNA