Cell differentiation is a unidirectional and irreversible process. During early development, pluripotent embryonic stem cells can generate every cell type of the organism. Yet, this ability is progressively restricted, especially during the formation of the three embryonic germ layers, the endoderm, the mesoderm and the ectoderm. Within these layers, cells see their differentiation potential reduced and can only give rise to certain cell types, specific to each layer. However, a cell population called cranial neural crest cells (CNCC) does not respect this rule. Originating from the ectoderm, CNCC not only give rise to neurons and glial cells, but they also generate cell types such as facial bones and cartilages, tissues normally formed by cells originating from the mesoderm.
CNCC remarkable plasticity is linked with the re-expression of pluripotency genes, which allows them to increase their differentiation potential. In addition, pre-migratory CNCC carry positional information reflective of their spatial origin in the neuroepithelium. However, this identity is subsequently erased with migratory CNCC forming a transcriptionally homogenous population, which later re-diversifies as CNCC undergo commitment events.
By combining sequencing approaches with in vivo and in vitro functional validations, our project intends to understand the molecular mechanisms controlling CNCC plasticity during development and post-natal regeneration which represent fundamental questions in the fields of developmental biology, stem cell research and regenerative medicine. This knowledge will be essential to establish prototype procedures aiming at enhancing endogenous regenerative responses during tissue repair for treatments of several congenital craniofacial syndromes – which represent a third of all congenital malformations within human populations – that require heavy maxillo-facial surgeries and reconstruction for humans suffering traumatic injuries.
