Neuronal and glial cell biology

Abstract

Brain development and signaling are intimately linked to the form and function of constituent neuronal and glial cells. Recent advances in microscopy, the major tool of cell biologists, and methods for manipulating molecular signals have made this an area ripe for discovery. This issue of Current Opinion in Neurobiology highlights some recent advances. A focus of this issue is how axonal and dendritic arbors are shaped, directed by intrinsic and extrinsic cues being uncovered by powerful genetic experiments. Remarkably, axonal arbors undergo vigorous structural plasticity even in the adult brain. This is complemented by articles addressing morphogenetic processes involving highly specialized membranes, myelin, and photoreceptive membranes. Studies of fundamental neuronal and glial cell biology can have a major impact on understanding neurological disorders, as exemplified by the articles on opioid receptors in addiction and on a novel neurodegenerative proteinopathy. Axonal and dendritic arbors: development and adult plasticity Numerous families of attractive and repulsive contact-dependent and contact-independent axon guidance molecules have been identified, often initially from cell culture and invertebrate models. Understanding how such cues act together with neuronal activity to guide axon projections in the mammalian brain has best been achieved in the mouse olfactory system, as reviewed by Imai and Sakano. Sensory neurons in the olfactory epithelium express only one of a thousand odorant receptor genes, and sensory neurons expressing the same odorant receptor converge their axons onto the same small subset of glomeruli in the olfactory bulb. The basis for how odorant receptors direct such precise connectivity has been elusive until recently. Partly on the basis of elegant genetic experiments from their own group, Imai and Sakano discuss how axons utilize dorso-ventral positional information, odorant receptor-mediated cAMP signaling, and classic axon guidance molecules including neuropilins, Kirrels, and ephrin-As and EphAs for precise navigation. A key concept is the idea that odorant receptor function via cAMP and neuronal activity regulate the expression level of specific axon guidance molecules in individual sensory neurons. Axonal arbors are not fixed in the adult, but rather undergo a remarkable degree of structural plasticity, as revealed in recent studies complementing assays of dendritic spine plasticity. Gogolla, Galimberti, and Caroni discuss the evidence for, mechanisms of, and implications of plasticity of axon sidebranches, en-passant boutons, and terminaux boutons. Although most axon boutons are stable for months, an intermingled proportion depending on the specific cell type and target region form anew or disappear, perhaps undergoing several cycles of remodeling during the lifetime of an organism. Remodeling is greatest during crucial periods of development but has also been directly visualized in adult mouse and monkey cortex in vivo by two-photon imaging of GFP-labeled axons. Given the large synaptic sampling territory of an individual axon, such plasticity can significantly alter microcircuitry and is no doubt linked to experience-related learning, memory, and adaptation, as insightfully conveyed by Gogolla, Galimberti, and Caroni. Less well studied than axon guidance, dendritic morphogenesis equally controls neuronal connectivity. Much of our insight into molecular mechanisms controlling dendrite arborization comes from Drosophila genetic screens and is adeptly reviewed by Gao. As exemplified by mammalian Purkinje neurons and Drosophila dendritic arborization neurons, dendrite arbor is often considered a defining characteristic of a neuron. Thus it is not surprising that transcriptional regulatory networks control many aspects of dendrite arborization. The link between transcriptional networks and surface molecules such as cadherins and semaphorins that regulate dendrite targeting is one active area of investigation. Exciting recent discoveries include the role of Tricornered-kinase/Furry signaling in dendritic tiling, nonredundant coverage by sister neurons, and the role of Down’s syndrome cell adhesion molecule (Dscam) homophilic adhesion in selfavoidance, repulsion between sister branches of a single neuron.