The Role of Imprinted Grb10 in Brain and Behavior (360G-Wellcome-105218_Z_14_Z)

The imprinted gene Grb10 is subject to epigenetic regulation leading to tissue specific differential parental-allelic expression. While the paternal allele is expressed exclusively in the CNS, the maternal allele is excluded from the CNS (and expressed in many non-CNS tissues) [1, 2]. The maternal allele is involved in aspects of development [3], and is thought to be key for coordinating the maternal-pup physiologies [4]. However, other than our original observation of a role in social dominance behaviour [1], very little is known about the brain and behavioural function of paternal Grb10. This project will examine aspects of neural function at the molecular, cellular and behavioural level. Specifically, cellular and molecular analyses will focus on examining the neurogenic potential of Grb10KO ES cells and, separately, the phenotype of cells with CRISPR altered epigenetic regulation of Grb10. We will aim to use these neural findings, and previous studies [1], to guide the exploration of a number of other behaviours in Grb10KO mice, including aspects of cognition. Finally, we will explore the interaction of maternal diet whilst pregnant and subsequent Grb10 regulation and expression in offspring brain.