Eph/Ephrin Signaling Controls Progenitor Identities In The Ventral Spinal Cord

Julien Laussu,Christophe Audouard,Poincyane Assis-Nascimento,Cathy Soula,Nathalie Escalas,Anthony Kischel,Daniel J Liebl,Alice Davy

doi:10.1186/s13064-017-0087-0

Abstract

BackgroundIn the vertebrate spinal cord, motor neurons (MN) are generated in stereotypical numbers from a pool of dedicated progenitors (pMN) whose number depends on signals that control their specification but also their proliferation and differentiation rates. Although the initial steps of pMN specification have been extensively studied, how pMN numbers are regulated over time is less well characterized.ResultsHere, we show that ephrinB2 and ephrinB3 are differentially expressed in progenitor domains in the ventral spinal cord with several Eph receptors more broadly expressed. Genetic loss-of-function analyses show that ephrinB2 and ephrinB3 inversely control pMN numbers and that these changes in progenitor numbers correlate with changes in motor neuron numbers. Detailed phenotypic analyses by immunostaining and genetic interaction studies between ephrinB2 and Shh indicate that changes in pMN numbers in ephrin mutants are due to alteration in progenitor identity at late stages of development.ConclusionsAltogether our data reveal that Eph:ephrin signaling is required to control progenitor identities in the ventral spinal cord.

Highlights

In the vertebrate spinal cord, motor neurons (MN) are generated in stereotypical numbers from a pool of dedicated progenitors whose number depends on signals that control their specification and their proliferation and differentiation rates
Concerning B-type ephrin ligands, in situ hybridization at different developmental stages reveals that while Efnb1 is not expressed at significant levels in progenitors of the ventral spinal cord (Fig. 1h-j), both Efnb2 and Efnb3 are expressed in subsets of these cells
Because Efnb2 and Efnb3 were expressed in distinct progenitor domains of the spinal cord, we asked whether these corresponded to progenitors with distinct identities, namely progenitors of motor neurons (pMNs) progenitors expressing Olig2 and p3 progenitors expressing Nkx2.2

Summary

Introduction

In the vertebrate spinal cord, motor neurons (MN) are generated in stereotypical numbers from a pool of dedicated progenitors (pMN) whose number depends on signals that control their specification and their proliferation and differentiation rates. As for other neuronal subtypes, the production of stereotyped numbers of MN requires the integration of different processes such as specification and proliferation of progenitors, followed by cell cycle exit and differentiation [1] While these processes are common to the genesis of all neuronal subtypes throughout the central nervous system, one distinguishing feature of MN development is the fact that progenitor specification is dependent on their spatial organization within the neural tube. The vertebrate neural tube is organized along its dorsoventral axis in different progenitor domains which first give rise to distinct neuronal subtypes and later on to subtypes of Laussu et al Neural Development (2017) 12:10 size of progenitor domains as the tissue grows are less well understood These mechanisms include maintenance of progenitor identities [4, 7, 8] as well as control of proliferation and differentiation rates that vary between progenitor types and over time [9]. Mechanisms such as cell sorting have been shown to participate in defining and/or maintaining domain boundaries indirectly contributing to pattern progenitor domains [10,11,12,13]

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