Funding outcome

All cells in our body start off with identical DNA, but the cells in each organ or tissue need to express a unique combination of genes to develop and function properly. Inside our cells, DNA is stored and regulated with the help of proteins, together forming a complex called chromatin. One type of such a protein is called a chromatin remodeler, which marks certain genes to be turned on or turned off, regulating their expression. This makes them very important for organ development. One chromatin remodeler can be responsible for regulating many genes, so a malfunction in that protein can have widespread effects on the body. KBG syndrome is a rare neurodevelopmental disorder, with symptoms such as distinctive facial features, developmental delays, intellectual disability, and autism. It is caused by a mutation in a gene called Ankrd11, which is a chromatin remodeler responsible for regulating genes in the neural crest, an embryonic tissue that will become the peripheral nervous system, cardiovascular system and the skull. My project focuses on finding if mutations in Ankrd11 dysregulate the formation of the vascular system in the body and brain during development, using a mouse model. Brain blood vessels release signals that control the development of other types of brain cells, such as neurons. If the brain blood vessels are improperly formed, it may cause abnormal development throughout the brain, which may contribute to impaired brain function. I will use resin casts of a mouse cardiovascular system to visualize whole-body blood vessel development. I will use cell type specific staining of developing brain tissue to detect anomalies in the number and location of cells of the brain and brain blood vessels. This project will help us understand how a mutation in a single gene translates into the symptoms seen in KBG patients, which will help us better understand how to help children with the disorder