title: Hox transcription factors influence motoneuron identity through the integrated actions of both homeodomain and non-homeodomain regions.
abstract: BACKGROUND
  Hox transcription factors play a critical role in the specification of motoneuron subtypes within the spinal cord. Our previous work showed that two orthologous members of this family, Hoxd10 and Hoxd11, exert opposing effects on motoneuron development in the lumbosacral (LS) spinal cord of the embryonic chick: Hoxd10 promotes the development of lateral motoneuron subtypes that project to dorsal limb muscles, while Hoxd11 represses the development of lateral subtypes in favor of medial subtypes that innervate ventral limb muscles and axial muscles. The striking degree of homology between the DNA-binding homeodomains of Hoxd10 and Hoxd11 suggested that non-homeodomain regions mediate their divergent effects. In the present study, we investigate the relative contributions of homeodomain and non-homeodomain regions of Hoxd10 and Hoxd11 to motoneuron specification.
  
  
  RESULTS
  Using in ovo electroporation to express chimeric and mutant constructs in LS motoneurons, we find that both the homeodomain and non-homeodomain regions of Hoxd10 are necessary to specify lateral motoneurons. In contrast, non-homeodomain regions of Hoxd11 are sufficient to repress lateral motoneuron fates in favor of medial fates.
  
  
  CONCLUSIONS
  Together, our data demonstrate that even closely related Hox orthologues rely on distinct combinations of homeodomain-dependent and -independent mechanisms to specify motoneuron identity.
authors.affiliation: Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Mala
authors.initials: M
authors.lastname: Misra
authors.forename: Emily
authors.initials: E
authors.lastname: Sours
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lance-Jones
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002642:Chick Embryo / Q000196:embryology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D030161:Avian Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors