BBDIV

Cilia are conserved organelles, from protists to Human, displaying various sensory or motile functions. Ciliary defects are responsible for life threatening diseases in humans. Although very well conserved throughout evolution, cilia exhibit structural variations between cell types in a given organism and between organisms. Our hypothesis is that cilia diversity is established during the early stages of cilium assembly, when basal bodies (BB) dock to the plasma membrane to form the transition zone (TZ), a specialized structure of the ciliary base. Several sets of conserved proteins are involved in BB docking but variations of their functions between tissues were described and not all proteins have been identified yet. Our objectives are therefore to decipher and compare the molecular steps specifically required to generate different TZ architectures using model organisms as a stepping-stone to understand cilia diversity in mammalian cells. We propose to take advantage of representative distant models that recapitulate the different types of cilia seen in humans: Paramecium, Drosophila, that are highly amenable for functional studies, and mammalian cell lines. We will: i) characterize novel BB docking actors isolated from our previous screens; ii) precisely tackle and compare in different ciliary types the hierarchical assembly of these proteins during the successive steps of TZ assembly; iii) understand how each complex contributes to the conserved and diverse architectures of the TZ during the initiation of cilia assembly. This multi-disciplinary strategy, combining functional studies of a restricted set of novel candidate proteins with cutting-edge imaging approaches (Expansion microscopy and FIB-SEM) will provide important fundamental insights into the mechanisms that control the variations observed in ciliary base architecture. Our project will bring novel perspectives to understand the diverse outcomes of mutations in ciliary base components in ciliopathies.