摘要: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder that is thought to emerge very early in development. Cerebral overgrowth, which is clinically referred to as macrocephaly, is frequently observed in children with ASD, and brain imaging studies have reported increases in both gray- and white-matter volume (1⇓⇓⇓⇓–6). Children with these early signs of brain enlargement have been shown to be part of an ASD group with high probability of receiving a diagnosis (3, 5⇓–7). The presence of additional numbers of neurons and increased cortical thickness in the prefrontal cortex of the postmortem brain from ASD patients complement these clinical observations (8). Copy number variation (CNV) in the 16p region of chromosome 16 has been linked to ASD and can manifest in opposing head sizes. Deletion of 16p11.2, which is probably one of the most well-known CNVs linked to ASD, generally leads to macrocephaly, whereas duplications in this region have been associated with smaller head sizes (9⇓⇓–12). The cellular mechanisms that underlie these opposing phenotypes remain unknown. Considering that live human brain tissues are inaccessible to study the cellular mechanisms that are contributing to these phenomena, the advent of induced pluripotent stem cell (iPSC) technologies has propelled research on this front as it allows researchers to generate any type of cell from human skin or blood. In PNAS, Li et al. take advantage of such an approach to explore the cellular mechanisms that could be involved in gray- and white-matter enlargement related to ASD (13). Here, iPSCs from a cohort of 16p11.2 deletion and duplication carriers were used to derive specific cellular models of the developing brain, in particular neural stem cells (NPCs), the precursors that will continue to form the cells of the gray … [↵][1]1To whom correspondence may be addressed. Email: sschafer{at}salk.edu or gage{at}salk.edu. [1]: #xref-corresp-1-1