title: Parallel Pbx-Dependent Pathways Govern the Coalescence and Fate of Motor Columns.
abstract: The clustering of neurons sharing similar functional properties and connectivity is a common organizational feature of vertebrate nervous systems. Within motor networks, spinal motor neurons (MNs) segregate into longitudinally arrayed subtypes, establishing a central somatotopic map of peripheral target innervation. MN organization and connectivity relies on Hox transcription factors expressed along the rostrocaudal axis; however, the developmental mechanisms governing the orderly arrangement of MNs are largely unknown. We show that Pbx genes, which encode Hox cofactors, are essential for the segregation and clustering of neurons within motor columns. In the absence of Pbx1 and Pbx3 function, Hox-dependent programs are lost and the remaining MN subtypes are unclustered and disordered. Identification of Pbx gene targets revealed an unexpected and apparently Hox-independent role in defining molecular features of dorsally projecting medial motor column (MMC) neurons. These results indicate Pbx genes act in parallel genetic pathways to orchestrate neuronal subtype differentiation, connectivity, and organization.
authors: Neuroscience Institute and Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
authors: Olivia
authors: O
authors: Hanley
authors: Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
authors: Rediet
authors: R
authors: Zewdu
authors: Genome Technology Center, NYU Langone Medical Center, 550 First Avenue, New York, NY 10016, USA.
authors: Lisa J
authors: LJ
authors: Cohen
authors: Neuroscience Institute and Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
authors: Heekyung
authors: H
authors: Jung
authors: Neuroscience Institute and Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
authors: Julie
authors: J
authors: Lacombe
authors: Neuroscience Institute and Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
authors: Polyxeni
authors: P
authors: Philippidou
authors: Neuroscience Institute and Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
authors: David H
authors: DH
authors: Lee
authors: Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
authors: Licia
authors: L
authors: Selleri
authors: Neuroscience Institute and Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA. Electronic address: jeremy.dasen@nyumc.org.
authors: Jeremy S
authors: JS
authors: Dasen
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002642:Chick Embryo; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D018398:Homeodomain Proteins; C481797:Pbx1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C090466:proto-oncogene protein Pbx3; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse