Cilia are hair-like protrusions generated on eukaryotic cell membranes by the microtubule cytoskeleton. Functionally, cilia fall into two categories: motile cilia and primary cilia. Motile cilia act as motors propelling extracellular fluids, whereas primary cilia function as cellular antennae, detecting chemical, mechanical or optical signals.
In multicellular organisms, cilia functions are cell type-dependent. In humans, some examples of tissue-specific cilia functions include: (i) light sensing by retinal photoreceptor cilia; (ii) urine flow monitoring by kidney cilia; (iii) feeding hormone sensing by hypothalamic neuronal cilia; (iv) motile cilia clearing mucus from our throats; (v) sperm motile cilia, better known as flagella, propelling sperm for fertilization; or (vi) embryonic cilia responding to morphogens, like Hedgehog (Hh), that pattern our skeletons and nervous systems.
These examples, which are far from exhaustive, reveal the widespread importance of cilia for human health. Accordingly, cilia malfunction leads to diseases such as ciliopathies and cancer. Cilia-related cancer often results from overactivation of ciliary Hh signaling, as occurs in medulloblastoma or basal cell skin carcinoma. In contrast, loss of ciliary Hh signaling is typically associated with ciliopathies, congenital diseases caused by ciliary gene mutations. The most common ciliopathies are polycystic kidney disease (PKD), retinitis pigmentosa (RP), and primary ciliary dyskinesia (PCD). Most ciliopathies, however, are rare and affect multiple organs (eyes, kidneys, brain, heart, bone, body fat, ...).
Our team studies the molecular bases of rare ciliopathy syndromes, such as Joubert (JBTS), Bardet-Biedl (BBS), Ellis van Creveld (EvC) and Meckel-Gruber (MKS) syndromes. In all these, the causative mutations lead to a defective composition and function of primary cilia, thus leading to disease manifestations. Therefore, we focus on the following key questions: (i) molecular mechanisms underlying control of primary cilia composition and function; (ii) how these mechanisms go awry in ciliopathies; and (iii) how to potentially alleviate these ciliary defects.