title: Bcl11a is required for neuronal morphogenesis and sensory circuit formation in dorsal spinal cord development.
abstract: Dorsal spinal cord neurons receive and integrate somatosensory information provided by neurons located in dorsal root ganglia. Here we demonstrate that dorsal spinal neurons require the Krüppel-C(2)H(2) zinc-finger transcription factor Bcl11a for terminal differentiation and morphogenesis. The disrupted differentiation of dorsal spinal neurons observed in Bcl11a mutant mice interferes with their correct innervation by cutaneous sensory neurons. To understand the mechanism underlying the innervation deficit, we characterized changes in gene expression in the dorsal horn of Bcl11a mutants and identified dysregulated expression of the gene encoding secreted frizzled-related protein 3 (sFRP3, or Frzb). Frzb mutant mice show a deficit in the innervation of the spinal cord, suggesting that the dysregulated expression of Frzb can account in part for the phenotype of Bcl11a mutants. Thus, our genetic analysis of Bcl11a reveals essential functions of this transcription factor in neuronal morphogenesis and sensory wiring of the dorsal spinal cord and identifies Frzb, a component of the Wnt pathway, as a downstream acting molecule involved in this process.
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, 89081 Ulm, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: John
authors.forename: Heike
authors.initials: H
authors.lastname: Brylka
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiegreffe
authors.forename: Ruth
authors.initials: R
authors.lastname: Simon
authors.forename: Pentao
authors.initials: P
authors.lastname: Liu
authors.forename: René
authors.initials: R
authors.lastname: Jüttner
authors.forename: E Bryan
authors.initials: EB
authors.lastname: Crenshaw
authors.forename: Frank P
authors.initials: FP
authors.lastname: Luyten
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: Neal G
authors.initials: NG
authors.lastname: Copeland
authors.forename: Carmen
authors.initials: C
authors.lastname: Birchmeier
authors.forename: Stefan
authors.initials: S
authors.lastname: Britsch
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology* / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism
chemical_list: C407733:Bcl11a protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins