Expression and function of Nkx6.3 in vertebrate hindbrain

• Published in: Brain research Vol. 1222; pp. 42 - 50
• Main Authors: Hafler, Brian P, Choi, Michael Y, Shivdasani, Ramesh A, Rowitch, David H
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 30-07-2008; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Central nervous system; CNS development; Electroporation - methods; Embryo, Mammalian; Eye Proteins - genetics; Eye Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression - physiology; Gene Expression Regulation, Developmental - genetics; Homeobox transcription factor; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Homeodomain Proteins - physiology; Interneurons - metabolism; LIM-Homeodomain Proteins; Medullary reticular formation; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Neurology; Nkx6.1; Nkx6.3; Paired Box Transcription Factors - genetics; Paired Box Transcription Factors - metabolism; PAX6 Transcription Factor; Repressor Proteins - genetics; Repressor Proteins - metabolism; Rhombencephalon - cytology; Rhombencephalon - embryology; Rhombencephalon - metabolism; Rhombomere; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; V2 interneuron; Vertebrates: nervous system and sense organs; Homeobox transcription factor; Nkx6.3; CNS development; Nkx6.1; Rhombomere; Medullary reticular formation; V2 interneuron; Central nervous system; Reticular formation; Gene expression; Interneuron; Development; Transcription factor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.04.072

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.