ProjectThe respiratory tract epithelium: a protective ecosystem

About

The respiratory tract epithelium lines the nose, trachea, and bronchi. It is composed of different cell types that orchestrate mucociliary clearance to effectively protect the respiratory tract mucosa against various stressors (allergens, chemical compounds, bacteria, viruses, transformations, etc.). These cell types are produced through specific genetic programs, resulting in the differentiation of multiciliated epithelial cells, which have hundreds of motile cilia on their apical surface; mucus-secreting cells, capable of secreting a protective mucus that coats the epithelial surfaces; and various types of basal cells that play a role in anchoring and regenerating the epithelium. Any dysfunction affecting these cells can be associated with serious diseases such as asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis.
Our team is interested in the genetic differentiation programs that enable the construction of the respiratory tract epithelium. To study them, we have several primary human cell culture models capable of reproducing certain essential physiological conditions.
In 2011, we discovered the crucial role played by the miR-34/449 microRNA (miRNA) families in the differentiation of multiciliated cells (a process called multiciliogenesis), by blocking the cell cycle, the Notch pathway, and then the relocalization of the actin cytoskeleton. Surprisingly, several other molecules (CCNO, MCIDAS, CDC20B), also encoded by the same 5q11 genomic region in humans, have all been implicated in the mechanisms of multiciliogenesis. This is particularly true of CDC20B, which participates in the function of the deuterosome, a specialized cytoplasmic organelle that enables the multiplication of centrioles, an essential prerequisite for the biosynthesis of the multiple motile cilia of multiciliated cells in vertebrates. Our studies also focus on the molecular mechanisms controlling the expression of mucus-secreting cells.