The study of human genetic neurodevelopmental disorders (NDDs) is complicated by the inaccessibility of the relevant tissue for study: it is extremely rare to obtain post-surgical brain samples from patients, and the origins of disease often occur in-utero. The technologies of ex-vivo stem cell culture is a valuable tool to study embryonic development. Derived from the embryo and cultured under appropriate conditions, both embryonic stem and committed neural stem cells display multipotent features of the tissue they are derived from, and are licenced in-vitro with the properties of unlimited self-renewal. The subsequent differentiation of these cells recapitulate many aspects of in-vivo development and can be used to model embryonic brain development. Because of these attributes, and the ease of genetic and other manipulations afforded in-vitro, we have employed these models to assess the effects of gene mutations that underlie neurodevelopmental disorders. We have been able to assign neurodevelopmental functions to newly discovered novel genes, test the pathogenicity of variants of unknown significance, and identify aspects of brain development likely affected in patients harbouring deleterious mutations.