Development and Arealization of the Cerebral Cortex

• Published in: Neuron (Cambridge, Mass.) Vol. 103; no. 6; pp. 980 - 1004
• Main Authors: Cadwell, Cathryn R., Bhaduri, Aparna, Mostajo-Radji, Mohammed A., Keefe, Matthew G., Nowakowski, Tomasz J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.09.2019; Elsevier Limited
• Subjects: Animals; autism; brain development; Cerebral cortex; Cerebral Cortex - embryology; Cognitive ability; Deep Learning; Gene expression; Gene Expression Regulation, Developmental; Genotype & phenotype; Homology; human brain; Humans; Interneurons - cytology; Interneurons - metabolism; machine learning; Neural Inhibition; Neural networks; Neurodevelopmental disorders; neurogenesis; Neurogenesis - genetics; Neurogenesis - physiology; Neurons; Neurons - cytology; Neurons - metabolism; protocortex; protomap; serial homology; Single-Cell Analysis; Thalamus - embryology; brain development; cerebral cortex; human brain; protocortex; neural networks; neurogenesis; machine learning; autism; protomap; serial homology
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2019.07.009

Adult cortical areas consist of specialized cell types and circuits that support unique higher-order cognitive functions. How this regional diversity develops from an initially uniform neuroepithelium has been the subject of decades of seminal research, and emerging technologies, including single-cell transcriptomics, provide a new perspective on area-specific molecular diversity. Here, we review the early developmental processes that underlie cortical arealization, including both cortex intrinsic and extrinsic mechanisms as embodied by the protomap and protocortex hypotheses, respectively. We propose an integrated model of serial homology whereby intrinsic genetic programs and local factors establish early transcriptomic differences between excitatory neurons destined to give rise to broad “proto-regions,” and activity-dependent mechanisms lead to progressive refinement and formation of sharp boundaries between functional areas. Finally, we explore the potential of these basic developmental processes to inform our understanding of the emergence of functional neural networks and circuit abnormalities in neurodevelopmental disorders. Cadwell et al. review the early developmental processes that underlie arealization of the cerebral cortex, with a focus on recent single-cell transcriptomic studies, the interplay of intrinsic genetic programs and extrinsic signals, and implications for developmental of functional circuits.