La génétique moléculaire des neurocristopathies


Nicolas Pilon

Université du Québec à Montréal [UQAM]


Domaine :  santé de la mère, des enfants et des adolescents

Programme chercheurs-boursiers - Senior

Concours 2017-2018

Neurocristopathies form a specific group of rare genetic diseases that result from problems with neural crest cells (NCC). These vertebrate-specific cells migrate extensively from the neural tube (the central nervous system primordium) and are characterized by broad multipotency. Such characteristics allow NCC to colonize several regions of the developing embryo and generate a wide array of cell types such as peripheral neurons and glia, melanocytes, adrenal chromaffin cells, cranio-facial chondrocytes and osteoblasts as well as specific cell subsets of the heart, inner ear and thymus. Because of the large number of NCC 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, our work is aimed at 1) identifying new causative genes for neurocristopathies such as Hirschsprung disease, Waardenburg syndrome and CHARGE syndrome; 2) understanding the exact function of these genes in normal and pathological conditions; and 3) using this knowledge in order to develop new personalized therapeutic approaches. To this end, we use the mouse as a model organism and take advantage of the most recent methods of genomic modifications and analyses. Such studies are complemented by more classical techniques of molecular and cellular biology. And, through established collaborations with multiple researchers working in a clinical setting, we also take care to validate our findings in children affected by the studied neurocristopathy.