title: A role for midline closure in the reestablishment of dorsoventral pattern following dorsal hindbrain ablation.
abstract: The cellular and molecular study of dorsal neural tube ablation reported here demonstrates a critical role for midline closure in hindbrain repatterning. This was revealed by detailed analysis of the transcriptional response of two genes, Pax-3 and slug, during repair of the neural tube following ablation. The reexpression of Pax-3 appears to rely on a single surface ectoderm/neuroepithelial contact, while this is insufficient for reexpression of slug. In fact, slug up-regulation only occurred upon midline closure and, strikingly, corresponded to down-regulation of Pax-3. We examined whether a candidate dorsalizing molecule, Bmp-4, was responsible for this reciprocal regulation of Pax-3 and slug at midline closure. However, Bmp-4 was not reexpressed following ablation, indicating not only that it is not responsible for the observed repatterning but that it lies in regulatory pathways distinct from Pax-3 and slug. We additionally examined the expression of Pax-6, which, together with assessment of the pattern of cranial ganglia, roof plate morphology, and positioning of branchiomotor exit points, demonstrates that neural crest regeneration is accompanied by reestablishment of a normal dorsoventral pattern within the neural tube. Thus, both local and longer range patterning appears to be restored following ablation, which is reliant dorsally on midline closure of the neural tube.
authors.affiliation: Developmental Biology Unit, Institute of Child Health (University College London), Britain.
authors.forename: P
authors.initials: P
authors.lastname: Buxton
authors.forename: P
authors.initials: P
authors.lastname: Hunt
authors.forename: P
authors.initials: P
authors.lastname: Ferretti
authors.forename: P
authors.initials: P
authors.lastname: Thorogood
mesh_terms: D000818:Animals; D019521:Body Patterning; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics; D004475:Ectoderm; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D009432:Neural Crest / Q000502:physiology*; D000072041:PAX3 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000032:analysis; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins; D012249:Rhombencephalon / Q000196:embryology* / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D015291:Transforming Growth Factors / Q000235:genetics
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000072041:PAX3 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C081351:dorsalin 1 protein, Gallus gallus; C068686:Pax3 protein, mouse; D015291:Transforming Growth Factors