Glia outnumber neurons and are the most abundant cell type in the nervous system. Whereas neurons are the major carriers, transducers, and processors of information, glial cells, once considered mainly to play a passive supporting role, are now recognized for their active contributions to almost every aspect of nervous system development. Recently, insights from the invertebrate organism Drosophila melanogaster have advanced our knowledge of glial cell biology. In particular, findings on neuron-glia interactions via intrinsic and extrinsic mechanisms have shed light on the importance of glia during different stages of neuronal development. Here, we summarize recent advances in understanding the functions of Drosophila glia, which resemble their mammalian counterparts in morphology and function, neural stem-cell conversion, synapse formation, and developmental axon pruning. These discoveries reinforce the idea that glia are substantial players in the developing nervous system and further advance the understanding of mechanisms leading to neurodegeneration.Keywords: glia; neuronal development; Gcm; neurodegeneration; neural stem cell; synapse formation; axon pruning Conventionally, glia have been considered to play a passive supporting role due to a lack of electrical excitability for transducing information like neurons. Nonetheless, compelling evidence has demonstrated that glia participate actively in mediating a number of neuronal events such as axon guidance, peripheral axon ensheathment, and formation of the blood-brain barrier to protect the central nervous system (CNS) [1][2][3][4][5] . On the other hand, a tripartite model that includes glia has recently been proposed to revise the classical view of synaptic structure [6][7][8] . In addition to the presynaptic and postsynaptic compartments, adjacent glia, particularly mammalian astrocytes, are now envisioned as one of the major components integrating synaptic function by releasing gliotransmitters, promoting synapse formation, and regulating synaptic plasticity [9] .Intriguingly, studies from the invertebrate model organism Several recent articles have provided excellent overviews of the origin and development of glia [10][11][12][13][14] . In this review, we explicitly summarize glial functions that have emerged as key mechanisms in the regulation of neuronal development in Drosophila. We describe the distinct classes of Drosophila glia, followed by a discussion of how they modulate neural stem-cell behavior, an extrinsic regulatory step during the early stage of neural fate decision. Next, we discuss how glia secrete different factors to affect the development and function of the neuromuscular junction (NMJ). Finally, we compare the glia-derived two-step secretion/engulfment mechanism in NMJ remodeling with axon pruning of mushroom body (MB) γ-neurons.Altogether, these recent discoveries point to a significant role for glia during neuronal development, and provide novel insights into mechanisms leading to a destabilized state of the nervous system, as i...