Vsx1 Transiently Defines an Early Intermediate V2 Interneuron Precursor Compartment in the Mouse Developing Spinal Cord.

Cédric Francius,Olivier Schakman,Stéphanie Debrulle,Mengqing Xiang,Stavros Malas,Audrey Harris,Vincent Rucchin,Elena Panayiotou,Kamana Misra,Frédéric Clotman,Barbara Pelosi,Kara Ronellenfitch,Robert L Chow,María Hidalgo-Figueroa,Carlos Parras,Neoklis Makrides,Hessameh Hassani

doi:10.3389/fnmol.2016.00145

Abstract

Spinal ventral interneurons regulate the activity of motor neurons, thereby controlling motor activities. Interneurons arise during embryonic development from distinct progenitor domains distributed orderly along the dorso-ventral axis of the neural tube. A single ventral progenitor population named p2 generates at least five V2 interneuron subsets. Whether the diversification of V2 precursors into multiple subsets occurs within the p2 progenitor domain or involves a later compartment of early-born V2 interneurons remains unsolved. Here, we provide evidence that the p2 domain produces an intermediate V2 precursor compartment characterized by the transient expression of the transcriptional repressor Vsx1. These cells display an original repertoire of cellular markers distinct from that of any V2 interneuron population. They have exited the cell cycle but have not initiated neuronal differentiation. They coexpress Vsx1 and Foxn4, suggesting that they can generate the known V2 interneuron populations as well as possible additional V2 subsets. Unlike V2 interneurons, the generation of Vsx1-positive precursors does not depend on the Notch signaling pathway but expression of Vsx1 in these cells requires Pax6. Hence, the p2 progenitor domain generates an intermediate V2 precursor compartment, characterized by the presence of the transcriptional repressor Vsx1, that contributes to V2 interneuron development.

Highlights

During CNS development, the generation of numerous neuronal populations distinct in their functional properties, location and connectivity is a prerequisite for building circuitries that regulate complex behaviors like locomotion
We identify an early intermediate V2 precursor compartment characterized by the transient expression of the transcription factor Vsx1
At e9.5, OC-1 was present in V2a and V2b interneurons, as well as in other cells located lateral to the p2 progenitor domain (Figures 1C–C )

Summary

Introduction

During CNS development, the generation of numerous neuronal populations distinct in their functional properties, location and connectivity is a prerequisite for building circuitries that regulate complex behaviors like locomotion. These progenitor domains generate four cardinal classes of ventral interneurons termed V0 to V3 (Grillner and Jessell, 2009; Garcia-Campmany et al, 2010; Lu et al, 2015) These cardinal populations further diversify into numerous subsets characterized by distinct combinations of molecular markers, use of different neurotransmitters, specific projection patterns and differential contributions to the locomotor circuits (Moran-Rivard et al, 2001; Pierani et al, 2001; Karunaratne et al, 2002; Sapir et al, 2004; Al-Mosawie et al, 2007; Crone et al, 2008; Zhang et al, 2008; Zagoraiou et al, 2009; Panayi et al, 2010; Dougherty et al, 2013; Francius et al, 2013; Panayiotou et al, 2013; Azim et al, 2014; Zhang et al, 2014; Britz et al, 2015). This diversification process enables ventral interneuron subpopulations to ensure different aspects of the stereotypic pattern of locomotor activity, including left-right alternation (V0 + V2a), flexor-extensor alternation (V1 + V2b), speed (V1) and robustness and rhythmicity (V2d + V3; Lanuza et al, 2004; Gosgnach et al, 2006; Crone et al, 2008; Zhang et al, 2008, 2014; Dougherty et al, 2013; Talpalar et al, 2013; Azim et al, 2014; Britz et al, 2015)

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Conclusion