Targeted disruption of the homeobox gene Nkx2.9 reveals a role in development of the spinal accessory nerve.
The homeodomain-containing transcription factor Nkx2.9 is expressed in the ventralmost neural progenitor domain of the neural tube together with the related protein Nkx2.2 during early mouse embryogenesis. Cells within this region give rise to V3 interneurons and visceral motoneurons in spinal cord and hindbrain, respectively. To investigate the role of the Nkx2.9 gene, we generated a mutant mouse by targeted gene disruption. Homozygous mutant animals lacking Nkx2.9 were viable and fertile with no apparent morphological or behavioral phenotype. The distribution of neuronal progenitor cells and differentiated neurons in spinal cord was unaffected in Nkx2.9-deficient animals. This finding is in contrast to Nkx2.2-null mutants, which have been shown to exhibit ventral to dorsal transformation of neuronal cell fates in spinal cord. Our results suggest that specification of V3 interneurons in the posterior CNS does not require Nkx2.9, most probably because of functional redundancy with the co-expressed Nkx2.2 protein. In hindbrain, however, absence of Nkx2.9 resulted in a significantly altered morphology of the spinal accessory nerve (XIth), which appeared considerably shorter and thinner than in wild-type animals. Consistent with this phenotype, immature branchial motoneurons of the spinal accessory nerve, which normally migrate from a ventromedial to a dorsolateral position within the neural tube, were markedly reduced in Nkx2.9-deficient embryos at E10.5, while ventromedial motor column cells were increased in numbers. In addition, the vagal and glossopharyngeal nerves appeared abnormal in approximately 50% of mutant embryos, which may be related to the observed reduction of Phox2b expression in the nucleus ambiguus of adult mutant mice. From these observations, we conclude that Nkx2.9 has a specific function in the hindbrain as determinant of the branchial motoneuron precursor cells for the spinal accessory nerve and possibly other nerves of the branchial-motor column. Like other Nkx genes expressed in the CNS, Nkx2.9 seems to be involved in converting positional information into cell fate decisions.
Pabst
Oliver
O
Department of Cell and Molecular Biology, Institute of Biochemistry and Biotechnology, Technical University of Braunschweig, 38106 Braunschweig, Germany.
Rummelies
Janin
J
Winter
Barbara
B
Arnold
Hans-Henning
HH
D000055:Accessory Nerve / Q000196:embryology*; D000818:Animals; D001933:Brain Stem / Q000033:anatomy & histology; D002454:Cell Differentiation / Q000502:physiology; D018390:Gene Targeting; D017930:Genes, Reporter; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013116:Spinal Cord / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715627:Nkx2-2 protein, mouse; C112924:Nkx2-9 protein, mouse; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors