Grant: Operating Grant

During embryonic development, the process of neurulation is the first step toward establishment of the nervous system. It involves specific determinants of anterior (brain) and posterior (spinal cord) fates. In the posterior embryo, the first step of neurulation involves the generation of a sheet of cells called the neural plate. Through different processes, the neural plate is then shaped in a closed neural tube, the spinal cord precursor. From the dorsal neural tube, a specific subpopulation of cells, called the neural crest cells, emigrate to generate the peripheral nervous system. These cells have stem cell properties allowing them to also contribute other specialized cell types such as pigment cells (melanocytes), some hormone-producing cells and some muscle cells of the cardio-vascular system. Problems affecting neural tube closure as well as neural crest cell development are the cause of many birth defects or genetic syndromes, such as spina bifida and aganglionic megacolon. Misregulations of neural crest cell development are also responsible of many cancers from childhood to adulthood such as neuroblastoma and malignant melanoma. A better understanding of neural tube formation and neural crest cell function at the molecular level is therefore required to allow identification of predisposed individuals as well as facilitating diagnosis and treatment of the related illnesses. Members of the Cdx protein family (Cdx1, Cdx2 and Cdx4) are specific determinants of posterior fates and they are active in the early developing spinal cord, starting well before the formation of a neural tube. They are also active in pre-migratory and early migratory neural crest cells. However, the Cdx function in these cells is still not clear because of a lack of a good experimental model. Using innovative approaches, the purpose of this project is to determine Cdx function in the process of neural tube formation as well as in the specification of neural crest cells.