title: Hox3 genes coordinate mechanisms of genetic suppression and activation in the generation of branchial and somatic motoneurons.
abstract: In the developing hindbrain, the functional loss of individual Hox genes has revealed some of their roles in specifying rhombomere (r) identity. However, it is unclear how Hox genes act in concert to confer the unique identity to multiple rhombomeres. Moreover, it remains to be elucidated how these genes interact with other transcriptional programs to specify distinct neuronal lineages within each rhombomere. We demonstrate that in r5, the combined mutation of Hoxa3 and Hoxb3 result in a loss of Pax6- and Olig2-expressing progenitors that give rise to somatic motoneurons of the abducens nucleus. In r6, the absence of any combination of the Hox3 paralogous genes results in ectopic expression of the r4-specific determinant Hoxb1. This ectopic expression in turn results in the differentiation of r4-like facial branchiomotoneurons within this rhombomere. These studies reveal that members of the Hox1 and Hox3 paralogous groups participate in a 'Hox code' that is necessary for coordinating both suppression and activation mechanisms that ensure distinction between the multiple rhombomeres in the developing hindbrain.
authors.affiliation: Howard Hughes Medical Institute, Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Gary O
authors.initials: GO
authors.lastname: Gaufo
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Thomas
authors.forename: Mario R
authors.initials: MR
authors.lastname: Capecchi
mesh_terms: D000010:Abducens Nerve / Q000166:cytology / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002465:Cell Movement / Q000502:physiology; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D009046:Motor Neurons / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D029867:Xenopus Proteins; C101121:HOXB1 homeodomain protein; C078105:Hox 2.7 protein, Xenopus; C489830:Hoxa2 protein, Xenopus; C080331:Hoxa3 protein, mouse; C484113:Hoxd3 protein, mouse; C512773:Olig2 protein, mouse; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse