Gene regulatory mechanisms underlying development of human neural crest
Neural crest is a transient cell population that is ectodermal in origin, but upon delamination from the neural tube acquires a remarkably broad differentiation potential and ability to migrate throughout the body to give rise to craniofacial skeleton and connective tissue, peripheral nervous system, pigment cells, and certain cardiac structures. Aberrant neural crest development is associated with a broad variety of congenital malformations, known as neurocristopathies, which often manifest in deafness and complex craniofacial defects, and which include a large variety of syndromes, as well as non-syndromic manifestations, such as cleft lip and palate, one of the most common congenital defects.
Very little is known about molecular mechanisms facilitating remarkable developmental plasticity of the neural crest, in part due to the transient, migratory nature of these cells. Indeed, regulatory events that accompany neural crest formation occur at 3 to 6 weeks of human gestation and are largely inaccessible for studies in an embryonic context. To overcome this limitation we developed a human ESC-based in vitro model, which recapitulates gene expression, migratory potential and differentiation characteristics of the neural crest. Here we propose to use this model to study gene regulatory mechanisms underlying different steps of neural crest formation and their perturbations in disease.
Our research will provide insights into fundamental mechanisms of human development, generate tools for advancement of new stem cell therapies based on directed differentiation of stem cell populations, characterize novel human regulatory sequences that can be utilized in personalized medicine and enhance understanding of genetic basis of common congenital malformations, such as cleft lip/palate.
Other tangible and immediate benefits for the community include:
- contribution to the training of new workforce in human stem cell technologies
- creation of new intellectual property that would benefit local institution and by extension local community.
- boosting local economy since we buy our supplies from local vendors whenever possible.