Progress in understanding the development of the oligodendrocyte lineage is a cogent example of how development can transform our understanding learn more of diseases like MS, and other human disorders with prominent white matter injury including cerebral palsy, stroke, and spinal cord injury (Fancy et al., 2011). Speaking of “transformation,” recent studies suggest, unexpectedly, that oligodendrocytes serve as a cell of origin

for glioma (Liu et al., 2011). Indeed, both OPCs and glioma can invade and migrate through tissues and proliferate in response to oncogenic signals of the RAS pathway. Exploiting such parallels in oligodendrocyte biology and gliomagenesis might provide insights into the genesis and biological properties of

these deadly tumors as well as their therapy. Astrocytes are the most numerous cell type in the brain and a steady stream of work points to an increasingly wide spectrum of roles for these cells during development and in the mature CNS. Although the precise nature of astrocyte precursors remains poorly understood, radial glia comprise a substrate for generation and migration during development and may have additional roles in CNS organization (described below). During development, radial glial cells produce neuron, oligodendrocyte, and astrocyte precursors and then, finally, transform into astrocytes themselves (which explains why any cre recombinase fate map that includes even a transient stage of radial Talazoparib price glia expression will mark a subset of astrocytes). It has become clear from recent work that a proliferating nonradial glial cell (“intermediate astrocyte precursor”) serves to expand

local astrocyte populations in different CNS domains (Ge et al., 2012 and Tien et al., 2012). Classic astrocyte roles include structural and metabolic support, maintenance of the blood-brain barrier (BBB), regulation of cerebral blood flow, clearance of neurotransmitters at the synapses and maintaining ion balance, support of myelin structures in white matter tracts, and inflammatory because reactivity after injury. Recent studies indicate that astrocytes are working hastily in the trenches during neural circuit formation and fine-tuning of synapses. We now appreciate that astrocytes can potently promote synaptogenesis through expression of thrombospondins, Sparc, and glypicans to allow for initial neuron-neuron contact and probably subsequent fine-tuning (Allen et al., 2012, Christopherson et al., 2005 and Kucukdereli et al., 2011). Optimization of connectivity through synapse elimination can also be carried out directly by astrocyte engulfment of synapses through MerTK and MEGF10 (W.S. Chung and B. Barres, personal communication), a molecular event first described in Drosophila ( Awasaki et al., 2006), or through modulating C1Q/complement cascade-mediated removal of synapses by microglia ( Stevens et al., 2007).