title: Requirement for downregulation of kreisler during late patterning of the hindbrain.
abstract: Pattern formation in the hindbrain is governed by a segmentation process that provides the basis for the organisation of cranial motor nerves. A cascade of transcriptional activators, including the bZIP transcription factor encoded by the kreisler gene controls this segmentation process. In kreisler mutants, r5 fails to form and this correlates with abnormalities in the neuroanatomical organisation of the hindbrain. Studies of Hox gene regulation suggest that kreisler may regulate the identity as well as the formation of r5, but such a role cannot be detected in kreisler mutants since r5 is absent. To gain further insights into the function of kreisler we have generated transgenic mice in which kreisler is ectopically expressed in r3 and for an extended period in r5. In these transgenic mice, the Fgf3, Krox20, Hoxa3 and Hoxb3 genes have ectopic or prolonged expression domains in r3, indicating that it acquires molecular characteristics of r5. Prolonged kreisler expression subsequently causes morphological alterations of r3/r5 that are due to an inhibition of neuronal differentiation and migration from the ventricular zone to form the mantle layer. We find that these alterations in r5 correlate with an arrest of facial branchiomotor neurone migration from r4 into the caudal hindbrain, which is possibly due to the deficiency in the mantle layer through which they normally migrate. We propose that the requirement for the downregulation of segmental kreisler expression prior to neuronal differentiation reflects the stage-specific roles of this gene and its targets.
authors.affiliation: Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Theil
authors.forename: Linda
authors.initials: L
authors.lastname: Ariza-McNaughton
authors.forename: Miguel
authors.initials: M
authors.lastname: Manzanares
authors.forename: Jim
authors.initials: J
authors.lastname: Brodie
authors.forename: Robb
authors.initials: R
authors.lastname: Krumlauf
authors.forename: David G
authors.initials: DG
authors.lastname: Wilkinson
mesh_terms: D000818:Animals; D030161:Avian Proteins; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D016350:Leucine Zippers; D051258:MafB Transcription Factor; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009474:Neurons / Q000166:cytology / Q000502:physiology; D015513:Oncogene Proteins; D012249:Rhombencephalon / Q000196:embryology* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D030161:Avian Proteins; D004268:DNA-Binding Proteins; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D015513:Oncogene Proteins; D014157:Transcription Factors