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.

Target selection of proprioceptive and motor axon synapses on neonatal V1‐derived Ia inhibitory interneurons and Renshaw cells

“…This contrasts with RCs, which appear to be homogeneously derived from V1 interneurons (Sapir et al, 2004). Alternative ventral interneurons with ipsilateral inhibitory axons are derived from the V2b group (Al-Mosawie et al, 2007;Lundfald et al, 2007). The possible derivation of some populations of IaINs from the V2b group is currently under investigation.…”

“…Pitx2 neurons are also already recognizable in early embryos (E12) within the V0 population (Zagoraiou et al, 2009). V2 interneurons diversify into excitatory Chx10-positive V2a and inhibitory GATA3-positive V2b interneurons (Lundfald et al, 2007). Finally, V3 interneurons also diversify in embryo into two groups with distinct migration patterns becoming located in two different spinal cord regions (Zhang et al, 2008).…”

Firing and Cellular Properties of V2a Interneurons in the Rodent Spinal Cord

“…The V2a interneurons constitute a subpopulation of the V2 class and express Chx10. The Chx10 neurons are exclusively glutamatergic and project ipsilaterally (Al-Mosawie et al, 2007;Lundfald et al, 2007). Recently, we have shown that left-right alternation is disrupted in transgenic mice in which Chx10 neurons have been selectively ablated by diphtheria toxin A, whereas alternation between flexors and extensors on the same side remains intact (Crone et al, 2008).…”

Organization of Functional Synaptic Connections between Medullary Reticulospinal Neurons and Lumbar Descending Commissural Interneurons in the Neonatal Mouse

“…In the mouse spinal cord, two broad populations of excitatory INs have been identified by their intraspinal axonal trajectories and developmental expression of molecular markers: (1) ipsilaterally projecting INs that express the transcription factors HB9 (Hinckley et al, 2005;Wilson et al, 2005), Chx10 (AlMosawie et al, 2007;Lundfald et al, 2007), or Sim1 (Zhang et al, 2008; J. C. Glover, unpublished observations); and (2) contralaterally projecting INs (CINs) that express the transcription factors Evx1 Pierani et al, 2001;Lanuza et al, 2004) or Sim1 (Zhang et al, 2008;Hägglund et al, 2010). It is clearly established in the adult cat that excitatory CINs receive inputs from pontine reticulospinal neurons (Jankowska et al, 2009 and references therein).…”