01391nas a2200217   4500000000100000000000100001008004100002260001500043653001600058653002400074653003300098653001500131100001200146700001700158700001600175245004000191856005500231300000900286520086400295022001401159       2023                            d  c2023-07-2810aDevelopment10aFunctional genomics10aNeurodevelopmental disorders10aStem cells1 aYi Zhou1 aHongjun Song1 aGuo-li Ming00aGenetics of human brain development  uhttps://www.nature.com/articles/s41576-023-00626-5  a1-203 aBrain development in humans is achieved through precise spatiotemporal genetic control, the mechanisms of which remain largely elusive. Recently, integration of technological advances in human stem cell-based modelling with genome editing has emerged as a powerful platform to establish causative links between genotypes and phenotypes directly in the human system. Here, we review our current knowledge of complex genetic regulation of each key step of human brain development through the lens of evolutionary specialization and neurodevelopmental disorders and highlight the use of human stem cell-derived 2D cultures and 3D brain organoids to investigate human-enriched features and disease mechanisms. We also discuss opportunities and challenges of integrating new technologies to reveal the genetic architecture of human brain development and disorders.  a1471-0064