Unwrapping glial biology: Gcm target genes regulating glial development, diversification, and function

Glia are the most abundant cell type in the mammalian brain. They regulate neuronal development and function, CNS immune surveillance, and stem cell biology, yet we know surprisingly little about glia in any organism. Here we identify over 40 new Drosophila glial genes. We use glial cells missing (gcm) mutants and misexpression to verify they are Gcm regulated in vivo. Many genes show unique spatiotemporal responsiveness to Gcm in the CNS, and thus glial subtype diversification requires spatially or temporally restricted Gcm cofactors. These genes provide insights into glial biology: we show unc-5 (a repulsive netrin receptor) orients glial migrations and the draper gene mediates glial engulfment of apoptotic neurons and larval locomotion. Many identified Drosophila glial genes have homologs expressed in mammalian glia, revealing conserved molecular features of glial cells. 80% of these Drosophila glial genes have mammalian homologs; these are now excellent candidates for regulating human glial development, function, or disease.