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New insight into building our nervous system
The research, which appears in the journal Science, discovered that glia, a collection of non-neuronal cells that had long been regarded as passive support cells, are in fact vital to nerve-cell development in the brain.
"The results lead us to revise the often neuro-centric view of brain development to, now, appreciate the contributions of non-neuronal cells such as glia. Indeed, our study found that fundamental questions in brain development with regard to the timing, identity, and coordination of nerve cell birth can only be understood when the glial contribution is accounted for."
Vilaiwan M. Fernandes, Postdoctoral Fellow, New York University, Department of Biology, and lead author.
The brain is made up of two broad cell types, nerve cells — neurons, and glia — non-nerve cells that make up more than half the volume of the brain. Neurobiologists have tended to focus on neurons as they form networks that process information. However, given the sheer number of glia in the brain's cellular make-up, the researchers began to think that they might play a fundamental role in brain development.
To explore this idea, they examined the visual system of the fruit fly. This species serves as a powerful model organism for this kind of study as its visual system, like ours, creates repeated mini-circuits to detect and process light over the entire visual field of the fly. This dynamic process is of particular interest to scientists. As the brain (human or fly) develops, it must coordinate an increase of neurons in the retina with other neurons in distant regions of the brain.
NYU researchers found that coordination of nerve-cell development is achieved through a population of glia, which relay cues from the retina to the brain making cells in the brain become nerve cells.
"By acting as a signaling intermediary, glia exert precise control over not only when and where a neuron is born, but also the type of neuron it will develop into."
Claude Desplan Phd, Department of Biology, New York University, New York, New York, USA, and senior author.
Wiring up the eye
During development, sensory systems must build topographic maps by connecting neurons at different levels within a circuit. Fernandes et al. now open a window into how the Drosophila eye develops these maps (see the Perspective by Isaacman-Beck and Clandinin). The authors show that glial cells that ensheath axons relay cues from photoreceptors to induce the differentiation of the photoreceptor target field—the so-called lamina neurons—in the Drosophila visual system. Thus, glia can play an instructive role in differentiation, helping to direct the spatiotemporal patterning of neurogenesis.
Neuronal birth and specification must be coordinated across the developing brain to generate the neurons that constitute neural circuits. We used the Drosophila visual system to investigate how development is coordinated to establish retinotopy, a feature of all visual systems. Photoreceptors achieve retinotopy by inducing their target field in the optic lobe, the lamina neurons, with a secreted differentiation cue, epidermal growth factor (EGF). We find that communication between photoreceptors and lamina cells requires a signaling relay through glia. In response to photoreceptor-EGF, glia produce insulin-like peptides, which induce lamina neuronal differentiation. Our study identifies a role for glia in coordinating neuronal development across distinct brain regions, thus reconciling the timing of column assembly with that of delayed differentiation, as well as the spatiotemporal pattern of lamina neuron differentiation.
Co-authors are Zhuo Zhang, Amanda E. Jones, Matthew B. Renfrow, Marina N. Vassylyeva, Dmitry G. Vassylyev, Keith E. Giles and Yue Gu, UAB Department of Biochemistry and Molecular Genetics; Wei Wu and Yue Kang, Institute of Biophysics, Chinese Academy of Sciences, Beijing; Jinman Kim and Woojin An, University of Southern California Department of Biochemistry and Molecular Biology; Xiaobao Bi and Chuan-Fa Liu, Nanyang Technological University, Singapore; Ivan K. Popov, UAB Department of Cell, Developmental and Integrative Biology; Dongquan Chen, UAB Division of Preventive Medicine and the UAB Comprehensive Cancer Center; Ashwath Kumar and Yuhong Fan, School of Biological Sciences, Georgia Institute of Technology; and Yufeng Tong, University of Toronto, Toronto, Canada.
The research was supported, in part, by a grant from the National Institutes of Health (EY13012).
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This is a confocal micrograph of a developing fruit fly visual system. Development of the retina (TOP) is coordinated with development of the optic lobe (SPHERE BELOW) region. All neurons are marked in yellow and their axon projections in cyan (greenish-blue); magenta (a light purplish red) in the optic lobe, marks the specific region of the brain where neuronal differentiation is regulated by glia. For a time-lapse movie of a fruit fly visual system developing over the course of six hours, please click here.