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  • Gene-environmental regulati...
    Prince, Gabrielle S.; Reynolds, Molly; Martina, Verdion; Sun, HaoSheng

    Trends in genetics, 06/2024, Volume: 40, Issue: 6
    Journal Article

    The postnatal brain undergoes chromatin and transcriptional changes that underlie functional maturation (e.g., electrophysiological properties, morphology, connectivity, network activity) across the lifespan. While these changes are observed across the animal kingdom, changes associated with maturation, including timing, are often neuron-type, brain-region, and species specific.Sensory stimulus coordination of neuronal activity and cross-modal neurotransmission is one mechanism by which the external environment regulates neuronal maturation.Neuronal activity controls the molecular changes underlying neuronal maturation by regulating transcriptional and chromatin factors.Aspects of postnatal neuronal maturation are regulated by cell-intrinsic sensory stimulus-independent genetic timer cascades. These mechanisms are intertwined with cell-extrinsic mechanisms to control maturation. Embryonic neurodevelopment, particularly neural progenitor differentiation into post-mitotic neurons, has been extensively studied. While the number and composition of post-mitotic neurons remain relatively constant from birth to adulthood, the brain undergoes significant postnatal maturation marked by major property changes frequently disrupted in neural diseases. This review first summarizes recent characterizations of the functional and molecular maturation of the postnatal nervous system. We then review regulatory mechanisms controlling the precise gene expression changes crucial for the intricate sequence of maturation events, highlighting experience-dependent versus cell-intrinsic genetic timer mechanisms. Despite significant advances in understanding of the gene-environmental regulation of postnatal neuronal maturation, many aspects remain unknown. The review concludes with our perspective on exciting future research directions in the next decade. Embryonic neurodevelopment, particularly neural progenitor differentiation into post-mitotic neurons, has been extensively studied. While the number and composition of post-mitotic neurons remain relatively constant from birth to adulthood, the brain undergoes significant postnatal maturation marked by major property changes frequently disrupted in neural diseases. This review first summarizes recent characterizations of the functional and molecular maturation of the postnatal nervous system. We then review regulatory mechanisms controlling the precise gene expression changes crucial for the intricate sequence of maturation events, highlighting experience-dependent versus cell-intrinsic genetic timer mechanisms. Despite significant advances in understanding of the gene-environmental regulation of postnatal neuronal maturation, many aspects remain unknown. The review concludes with our perspective on exciting future research directions in the next decade.