Role of Connexin 43 in Cranial Neural Crest Cell Differentiation

点击翻译按钮获取中文摘要

Much of the face and skull is formed by a special type of stem cells, called cranial neural crest cells (CNCCs). These cells arise from the developing brain and migrate into the forming head where they change identity, or differentiate, into a variety of cell types such as bone and cartilage cells and neurons. Through their contribution to the sensory organs and jaws, the origin of CNCCs in vertebrates is considered the main driver of predatory feeding evolution. Given the functional importance of the structures formed by CNCCs, proper differentiation of these cells is crucial, and is coordinated by cell-cell communication. Cells can communicate through gap junctions, which are small channels between adjacent cells formed by proteins called connexins. The most common gap junction protein is connexin 43 (Cx43), and this protein is expressed in CNCCs and is important for their migration to the developing head. However, the role of Cx43 in CNCC differentiation remains obscure. Therefore, the main objective of our collaboration is to determine the role of Cx43 in CNCC differentiation using mouse and chick models. To accomplish this objective, we have developed a mouse model wherein Cx43 is removed specifically from neural crest cells, known here as Cx43cKO. As expected, skull shape is altered in Cx43cKO mice, and these shape changes are localized to regions derived from CNCCs. To determine the role of Cx43 in CNCC differentiation, we will compare gene expression within single cells of CNCC origin between Cx43cKO and control mice, providing a list of genes involved in this cellular process. To understand how these target genes mediate CNCC differentiation, we will use the chick model where we can experimentally manipulate genes of interest to rapidly evaluate gene function. These studies will provide answers to fundamental questions related to stem cell differentiation, and, more broadly, skull development and evolution, helping to put Canada at the forefront of this vibrant and expanding scientific field. Additionally, trainees will gain valuable professional and technical skills that will position them for successful employment in academia and industry, enhancing Canada's economy.