Funding outcome

Ankrd11 (ankyrin repeat domain 11) functions as a chromatin remodeler. Chromatin is the condensed structure of genomic DNA that impacts global gene expression. In turn, global gene expression regulates cell and organism function. Mutations in the Ankrd11 gene lead to KBG syndrome, which is a rare neurodevelopmental disorder that has been diagnosed in ~500 children worldwide. KBG syndrome patients have disrupted brain development, which affects both grey matter (nerve cells) and white matter (oligodendrocytes). Patients also display global developmental delay, autism, and intellectual disability. Our lab has shown that Ankrd11 regulates the formation of nerve cells during embryonic development. However, the role of Ankrd11 in oligodendrocyte (white matter) development is currently not known. This is an important question to address because oligodendrocytes are required for efficient neural communication and learning and can be targeted pharmacologically to restore proper cognition and behaviour. This project will determine the role of Ankrd11 in oligodendrocyte development from neural stem cells. To do this, we will use a KBG syndrome mouse model, where we will remove Ankrd11 specifically in neural stem cells during a developmental period when oligodendrocytes are generated. I will assess oligodendrocyte numbers and myelination in Ankrd11-deficient mice. I will also design and test a culture system, where future drug screening can be performed to rescue oligodendrocyte formation in vitro. The results of this project will offer better counselling to affected families and may inspire novel therapies for KBG syndrome and other similar neurodevelopmental disorders.