Building brains in a dish - using ES cells to understand brain development

It has recently been shown that embryonic stem (ES) cells grown under appropriate conditions in 3D cultures can give rise to structures termed cerebral organoids that closely resemble=le embryonic forebrains. This raises the exciting possibility that ES cell-derived cultures could be used to replace mouse embryos in studies of brain development, leading to a significant reduction of animals used in such studies. In this PhD project, the student will (I) establish a robust, reproducible protocol for the derivation of cerebral organoids from mouse ES cells. (ii) Carry out a detailed comparison of the phenotypes of cerebral organoids derived from Pax6, Foxg1 and Gli3 mutant ES cells with those seen in equivalent mouse embryos in vivo, including measuring of cell proliferation rates, differentiation, cell death and expression of key regulatory molecules. (iii)Use cerebral organoids to investigate the molecular mechanisms by which one or more of these transcription factors exert their effects - most likely using combined gain and loss of function studies to identify the roles of downstream targets of the transcription factor(s).