title: The homeodomain factor Gbx1 is required for locomotion and cell specification in the dorsal spinal cord.
abstract: Dorsal horn neurons in the spinal cord integrate and relay sensory information to higher brain centers. These neurons are organized in specific laminae and different transcription factors are involved in their specification. The murine homeodomain Gbx1 protein is expressed in the mantle zone of the spinal cord at E12.5-13.5, correlating with the appearance of a discernable dorsal horn around E14 and eventually defining a narrow layer in the dorsal horn around perinatal stages. At postnatal stages, Gbx1 identifies a specific subpopulation of GABAergic neurons in the dorsal spinal cord. We have generated a loss of function mutation for Gbx1 and analyzed its consequences during spinal cord development. Gbx1 (-/-) mice are viable and can reproduce as homozygous null mutants. However, the adult mutant mice display an altered gait during forward movement that specifically affects the hindlimbs. This abnormal gait was evaluated by a series of behavioral tests, indicating that locomotion is impaired, but not muscle strength or motor coordination. Molecular analysis showed that the development of the dorsal horn is not profoundly affected in Gbx1 (-/-) mutant mice. However, analysis of terminal neuronal differentiation revealed that the proportion of GABAergic inhibitory interneurons in the superficial dorsal horn is diminished. Our study unveiled a role for Gbx1 in specifying a subset of GABAergic neurons in the dorsal horn of the spinal cord involved in the control of posterior limb movement.
authors.affiliation: Mouse Clinical Institute / Institut Clinique de la Souris, PHENOMIN, GIE CERBM, Illkirch Cedex, France.
authors.forename: Hamid
authors.initials: H
authors.lastname: Meziane
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch Cedex, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Fraulob
authors.affiliation: Mouse Clinical Institute / Institut Clinique de la Souris, PHENOMIN, GIE CERBM, Illkirch Cedex, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Riet
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch Cedex, France.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Krezel
authors.affiliation: Mouse Clinical Institute / Institut Clinique de la Souris, PHENOMIN, GIE CERBM, Illkirch Cedex, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Selloum
authors.affiliation: DFG-Center for Regenerative Therapies / Cluster of Excellence, and Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Geffarth
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", Naples, Italy.|IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Acampora
authors.affiliation: Mouse Clinical Institute / Institut Clinique de la Souris, PHENOMIN, GIE CERBM, Illkirch Cedex, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Hérault
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", Naples, Italy.|IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Simeone
authors.affiliation: DFG-Center for Regenerative Therapies / Cluster of Excellence, and Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Brand
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Dollé
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch Cedex, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Rhinn
keywords: GABAergic neurons; Gbx genes; Locomotion; Mouse mutant; Spinal cord