Different levels of repressor activity assign redundant and specific roles to Nkx6 genes in motor neuron and interneuron specification.
Specification of neuronal fate in the vertebrate central nervous system depends on the profile of transcription factor expression by neural progenitor cells, but the precise roles of such factors in neurogenesis remain poorly characterized. Two closely related transcriptional repressors, Nkx6.2 and Nkx6.1, are expressed by progenitors in overlapping domains of the ventral spinal cord. We provide genetic evidence that differences in the level of repressor activity of these homeodomain proteins underlies the diversification of interneuron subtypes, and provides a fail-safe mechanism during motor neuron generation. A reduction in Nkx6 activity further permits V0 neurons to be generated from progenitors that lack homeodomain proteins normally required for their generation, providing direct evidence for a model in which progenitor homeodomain proteins direct specific cell fates by actively suppressing the expression of transcription factors that direct alternative fates.
Vallstedt
A
A
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, S-171 77, Stockholm, Sweden.
Muhr
J
J
Pattyn
A
A
Pierani
A
A
Mendelsohn
M
M
Sander
M
M
Jessell
T M
TM
Ericson
J
J
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002642:Chick Embryo; D005136:Eye Proteins; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins / Q000235:genetics*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology; D029961:Zebrafish Proteins
C103403:Dbx1 protein, mouse; C103404:Dbx2 protein, mouse; D005136:Eye Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C491328:Nkx6-1 protein, mouse; C436827:Nkx6.2 protein, vertebrate; D000071841:PAX6 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C497322:Pax7 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins