What Happens When It Goes Wrong? Using Human Genetics to Understand Human Brain Development and Evolution

This chapter explores what happens when the development of the cerebral cortex goes awry. It presents results on work with CHMP1A mutations, which highlight the importance of specialized cell-to-cell communication via extracellular vesicles in cortical development and function. It reviews genetic causes of microcephaly, with an emphasis on centrosomal proteins, and presents novel insights about cortical evolution shown using a ferret model of microcephaly caused by ASPM loss of function. It reviews recent work to identify noncoding mutations that cause brain malformations, which has expanded understanding of cortical development beyond protein-coding genes. These three examples illustrate general principles of cortical growth and function (cellular communication and synaptic plasticity, evolution, and utilization of large data sets), made possible by recent advances in DNA sequencing technology.