title: Satb2 Is Required for the Development of a Spinal Exteroceptive Microcircuit that Modulates Limb Position.
abstract: Motor behaviors such as walking or withdrawing the limb from a painful stimulus rely upon integrative multimodal sensory circuitry to generate appropriate muscle activation patterns. Both the cellular components and the molecular mechanisms that instruct the assembly of the spinal sensorimotor system are poorly understood. Here we characterize the connectivity pattern of a sub-population of lamina V inhibitory sensory relay neurons marked during development by the nuclear matrix and DNA binding factor Satb2 (ISR(Satb2)). ISR(Satb2) neurons receive inputs from multiple streams of sensory information and relay their outputs to motor command layers of the spinal cord. Deletion of the Satb2 transcription factor from ISR(Satb2) neurons perturbs their cellular position, molecular profile, and pre- and post-synaptic connectivity. These alterations are accompanied by abnormal limb hyperflexion responses to mechanical and thermal stimuli and during walking. Thus, Satb2 is a genetic determinant that mediates proper circuit development in a core sensory-to-motor spinal network.
authors.affiliation: Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA, 92037, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Hilde
authors.affiliation: Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA, 92037, USA.
authors.forename: Ariel J
authors.initials: AJ
authors.lastname: Levine
authors.affiliation: Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA, 92037, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hinckley
authors.affiliation: Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA, 92037, USA.
authors.forename: Marito
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA, 92037, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Montgomery
authors.affiliation: Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA, 92037, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Gullo
authors.affiliation: Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA, 92037, USA.
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Driscoll
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Department of Cellular and Molecular Immunology, 79108 Freiburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grosschedl
authors.affiliation: Department of Orofacial Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kohwi
authors.affiliation: Department of Orofacial Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Terumi
authors.initials: T
authors.lastname: Kohwi-Shigematsu
authors.affiliation: Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA, 92037, USA. Electronic address: pfaff@salk.edu.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Pfaff
mesh_terms: D000818:Animals; D005121:Extremities / Q000502:physiology*; D007395:Interneurons / Q000502:physiology; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009434:Neural Pathways / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D012018:Reflex / Q000502:physiology; D011984:Sensory Receptor Cells / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D016138:Walking / Q000502:physiology*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C501473:SATB2 protein, mouse; D014157:Transcription Factors