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Neuronal guidance genes in health and diseases

Protein & Cell 2023年第4期14卷 238-261页

作者： Junichi Yuasa-Kawada Mariko Kinoshita-Kawada yoshio tsuboi Jane Y.Wu Department of Neurology Fukuoka University7.451 NanakumaJohnan.kuFukuoka 814-0180Japan Department of Neurology Center for Genetic MedicineLurie Cancer CenterNorthwestern University Feinberg School of MedicineWard Building Box 6117303E.Chicago AvenueChicagoIlinois 60611.USA

Neurons migrate from their birthplaces to the destinations,and extending axons navigate to their synaptic targets by sensing various extracellular cues in spatiotemporally controlled manners.These evolutionally conserved guidance cues and their receptors regulate multiple aspects of neural development to establish the highly complex nervous system by mediating both short-and long-range cell-cell communications.Neuronal guidance genes(encoding cues,receptors,or downstream signal transducers)are critical not only for development of the nervous system but also for synaptic maintenance,remodeling,and function in the adult brain.One emerging theme is the combinatorial and complementary functions of relatively limited classes of neuronal guidance genes in multiple processes,including neuronal migration,axonal guidance,synaptogenesis,and circuit formation.Importantly,neuronal guidance genes also regulate cell migration and cell-cell communications outside the nervous system.We are just beginning to understand how cells integrate multiple guidance and adhesion signaling inputs to determine overall cellular/subcellular behavior and how aberrant guidance signaling in various cell types contributes to diverse human diseases,ranging from developmental,neuropsychiatric,and neurodegenerative disorders to cancer metastasis.We review classic studies and recent advances in understanding signaling mechanisms of the guidance genes as well as their roles in human diseases.Furthermore,we discuss the remaining chalienges and therapeutic potentials of modulating neuronal guidance pathways in neural repair.

关键词： axon guidance neuronal migration synaptogenesis neural circuit formation neural mapping cell-cell communications angiogenesis organogenesis cancermetastasis

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