The effect of glia-glia interactions on oligodendrocyte precursor cell biology during development and in demyelinating diseases

Diego Clemente,Carolina Melero-Jerez,María Cristina Ortega,Fernando De Castro

doi:10.3389/fncel.2013.00268

Abstract

Oligodendrocyte precursor cells (OPCs) originate in specific areas of the developing central nervous system (CNS). Once generated, they migrate towards their destinations where they differentiate into mature oligodendrocytes. In the adult, 5–8% of all cells in the CNS are OPCs, cells that retain the capacity to proliferate, migrate, and differentiate into oligodendrocytes. Indeed, these endogenous OPCs react to damage in demyelinating diseases, like multiple sclerosis (MS), representing a key element in spontaneous remyelination. In the present work, we review the specific interactions between OPCs and other glial cells (astrocytes, microglia) during CNS development and in the pathological scenario of MS. We focus on: (i) the role of astrocytes in maintaining the homeostasis and spatial distribution of different secreted cues that determine OPC proliferation, migration, and differentiation during CNS development; (ii) the role of microglia and astrocytes in the redistribution of iron, which is crucial for myelin synthesis during CNS development and for myelin repair in MS; (iii) how microglia secrete different molecules, e.g., growth factors, that favor the recruitment of OPCs in acute phases of MS lesions; and (iv) how astrocytes modify the extracellular matrix in MS lesions, affecting the ability of OPCs to attempt spontaneous remyelination. Together, these issues demonstrate how both astroglia and microglia influence OPCs in physiological and pathological situations, reinforcing the concept that both development and neural repair are complex and global phenomena. Understanding the molecular and cellular mechanisms that control OPC survival, proliferation, migration, and differentiation during development, as well as in the mature CNS, may open new opportunities in the search for reparative therapies in demyelinating diseases like MS.

Highlights

Since the founding of neurosciences in the nineteenth century, neurons, the fast excitable cells of the nervous system, have captivated the attention of almost all the successive generations of researchers
The effect of astrocyte-derived PDGF-AA in stimulating oligodendrocyte precursor cells (OPCs) to either proliferate or differentiate into mature oligodendrocytes is influenced by the developmental stage of the progenitor cells (Raff et al, 1988), suggesting that in the optic nerve at least, PDGF-AA produced by astrocytes coordinates the timing of oligodendrogliogenesis (Durand and Raff, 2000)
ANOSMIN-1 We have studied the role of anosmin-1 in OPC development, another component of the ECM that is defective in the X-linked form of Kallmann syndrome (Soussi-Yanicostas et al, 2002; Dode and Hardelin, 2009)

Summary

INTRODUCTION

Since the founding of neurosciences in the nineteenth century, neurons, the fast excitable cells of the nervous system, have captivated the attention of almost all the successive generations of researchers. There is even more evidence that all the major types of glial cells fulfill activities beyond their classically accepted functions. The amount of data indicating that both astrocytes and microglia influences oligodendrocyte biology has grown steadily. Far from their classic roles as physical scaffolds and their participation in nutrient diffusion throughout the CNS, astrocytes have been shown to modulate neuronal activity and to respond to neurotransmitters in a clear and excitable manner (Araque and Navarrete, 2010). The purpose of the present work is to review the direct interactions between astrocytes/microglia and OPCs during normal CNS development and in pathological circumstances, focusing on multiple sclerosis (MS)

Glial cell interactions during remyelination

Occasional leukocytes