title: Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord.
abstract: The ventral spinal cord consists of interneuron groups arising from distinct, genetically defined, progenitor domains along the dorsoventral axis. Many of these interneuron groups settle in the ventral spinal cord which, in mammals, contains the central pattern generator for locomotion. In order to better understand the locomotor networks, we have used different transgenic mice for anatomical characterization of one of these interneuron groups, called V2 interneurons. Neurons in this group are either V2a interneurons marked by the postmitotic expression of the transcription factor Chx10, or V2b interneurons which express the transcription factors Gata2 and Gata3. We found that all V2a and most V2b interneurons were ipsilaterally projecting in embryos as well as in newborns. V2a interneurons were for the most part glutamatergic while V2b interneurons were mainly GABAergic or glycinergic. Furthermore, we demonstrated that a large proportion of V2 interneurons expressed the axon guidance molecule EphA4, a molecule previously shown to be important for correct organization of locomotor networks. We also showed that V2 interneurons and motor neurons alone did not account for all EphA4-expressing neurons in the spinal cord. Together, these findings enable a better interpretation of neural networks underlying locomotion, and open up the search for as yet unknown components of the mammalian central pattern generator.
authors.affiliation: Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
authors.forename: Line
authors.initials: L
authors.lastname: Lundfald
authors.forename: C Ernesto
authors.initials: CE
authors.lastname: Restrepo
authors.forename: Simon J B
authors.initials: SJ
authors.lastname: Butt
authors.forename: Chian-Yu
authors.initials: CY
authors.lastname: Peng
authors.forename: Steven
authors.initials: S
authors.lastname: Droho
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Endo
authors.forename: Hanns Ulrich
authors.initials: HU
authors.lastname: Zeilhofer
authors.forename: Kamal
authors.initials: K
authors.lastname: Sharma
authors.forename: Ole
authors.initials: O
authors.lastname: Kiehn
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D004622:Embryo, Mammalian; D007839:Functional Laterality; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D007395:Interneurons / Q000145:classification / Q000166:cytology / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism; D010641:Phenotype; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D014157:Transcription Factors / Q000235:genetics
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C094898:Lhx3 protein; D008164:Luminescent Proteins; C493270:Slc6a5 protein, mouse; D014157:Transcription Factors; C084059:Hb9 protein, mouse; D036122:Receptor, EphA4; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1