Grant: Project Grant

Neurocristopathies form a specific group of rare genetic diseases that result from problems with neural crest cells - a specific type of stem cells that migrate extensively from the neural tube (the central nervous system primordium) during embryogenesis. Such characteristics allow neural crest cells to colonize several regions of the developing embryo and generate a wide array of cell types such as peripheral neurons and glia, pigment cells, craniofacial bone cells as well as specific cell subsets of the heart, inner ear and thymus. Because of the large number of neural crest cell derivatives, distinct structures/cell types (isolated or in combination) are affected in each neurocristopathy. The most important issue in this research field is that the underlying genetic cause and associated pathogenic mechanism of most cases of neurocristopathy are poorly understood. To address this problem, we use the mouse as a model organism and take advantage of the state-of-the-art methods of genomic modifications and analyses. Such studies are complemented by more classical techniques of molecular and cellular biology. Importantly, through established collaborations with researchers working in a clinical setting, we also validate our findings in children affected by the studied neurocristopathy. Notably, this work allowed us to identify a new gene for which the mutation can cause CHARGE syndrome - a neurocristopathy with a very complex clinical presentation and which can be fatal for many young children. The main objective of the current project is to understand the function of this new gene (Fam172a) in both normal and pathological conditions. This work is expected to significantly improve the way children suffering from CHARGE syndrome - as well as their families - are currently being taken care of.