Centriole and ubiquitin pathway regulation of craniofacial development

National Institute Of Dental & Craniofacial Research

Investigators

Abstract

Over the past year the Craniofacial Development Unit has made progress in understanding how disruptions in centrioles/centrosomes contribute to impaired craniofacial development resulting in chronic disease and structural birth defects. We have identified early developmental events that precede and drive the emergence of craniofacial abnormalities, providing insight into how these perturbations ultimately result in the structural facial defects. In parallel, we have extended these studies into human stem cell–based models of congenital disorders to complement our animal models with New Approach Methodologies (NAMs) to better understand how different genetic changes can lead to tissue-specific outcomes and to develop novel human-based models to uncover relevant disease mechanisms. Additionally, we have carried out CRISPRi genetic screens to uncover pathways that regulate the formation, maintenance, and differentiation of craniofacial progenitor cells. These efforts have revealed both previously recognized and novel regulators, which will form the basis for future publications from our research group.