title: Expression and function of Nkx6.3 in vertebrate hindbrain.
abstract: Homeodomain transcription factors serve important functions in organogenesis and tissue differentiation, particularly with respect to the positional identity of individual cells. The Nkx6 subfamily controls tissue differentiation in the developing central nervous system where they function as transcriptional repressor proteins. Recent work indicates that Nkx6.3 is expressed in hindbrain V2 interneurons that co-express Nkx6.1, suggesting the possibility of functional redundancy. Here, we report that Nkx6.3 expression is specific to Chx10+ V2a interneurons but not to Gata3+ V2b interneurons of the hindbrain, and that Nkx6.3 expression appears to mark cells of the prospective medullary reticular formation. Molecular analysis of Nkx6.3 null embryonic mouse hindbrain did not reveal detectable defects in progenitor markers, motor neuron or V2 interneuron sub-types. Forced expression of Nkx6.3 and Nkx6.1 promote V2 interneuron differentiation in the developing chick hindbrain. These findings indicate Nkx6.3 function is dispensable for CNS development and lead to the proposal that absence of overt defects is due to functional compensation from a related homeodomain transcription factor.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Hafler
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Choi
authors.forename: Ramesh A
authors.initials: RA
authors.lastname: Shivdasani
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
mesh_terms: D000818:Animals; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; C532844:Nkx6-3 protein, mouse; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C088975:Vsx2 protein, mouse; C084059:Hb9 protein, mouse