title: Establishment of motor neuron-V3 interneuron progenitor domain boundary in ventral spinal cord requires Groucho-mediated transcriptional corepression.
abstract: BACKGROUND
  Dorsoventral patterning of the developing spinal cord is important for the correct generation of spinal neuronal types. This process relies in part on cross-repressive interactions between specific transcription factors whose expression is regulated by Sonic hedgehog. Groucho/transducin-like Enhancer of split (TLE) proteins are transcriptional corepressors suggested to be recruited by at least certain Sonic hedgehog-controlled transcription factors to mediate the formation of spatially distinct progenitor domains within the ventral spinal cord. The aim of this study was to characterize the involvement of TLE in mechanisms regulating the establishment of the boundary between the most ventral spinal cord progenitor domains, termed pMN and p3. Because the pMN domain gives rise to somatic motor neurons while the p3 domain generates V3 interneurons, we also examined the involvement of TLE in the acquisition of these neuronal fates.
  
  
  RESULTS
  A combination of in vivo loss- and gain-of-function studies in the developing chick spinal cord was performed to characterize the role of TLE in ventral progenitor domain formation. It is shown here that TLE overexpression causes increased numbers of p3 progenitors and promotes the V3 interneuron fate while suppressing the motor neuron fate. Conversely, dominant-inhibition of TLE increases the numbers of pMN progenitors and postmitotic motor neurons.
  
  
  CONCLUSIONS
  Based on these results, we propose that TLE is important to promote the formation of the p3 domain and subsequent generation of V3 interneurons.
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Todd
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lan-Chow-Wing
authors.forename: Adele
authors.initials: A
authors.lastname: Salin-Cantegrel
authors.forename: Anthony
authors.initials: A
authors.lastname: Cotter
authors.forename: Chrissandra J
authors.initials: CJ
authors.lastname: Zagami
authors.forename: Rita
authors.initials: R
authors.lastname: Lo
authors.forename: Stefano
authors.initials: S
authors.lastname: Stifani
mesh_terms: D000818:Animals; D002452:Cell Count; D019070:Cell Lineage; D002642:Chick Embryo; D002645:Chickens; D056970:Co-Repressor Proteins; D005136:Eye Proteins / Q000378:metabolism; D005799:Genes, Dominant / Q000235:genetics; D057809:HEK293 Cells; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D008954:Models, Biological; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D029961:Zebrafish Proteins
chemical_list: D056970:Co-Repressor Proteins; D005136:Eye Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D050505:Mutant Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; C499043:TLE1 protein, human; D014157:Transcription Factors; D029961:Zebrafish Proteins