The molecular aspects of primary cilia formation have started to emerge relatively recently. It is now appreciated that control of the initiation of ciliogenesis resides in the components of distal appendages (CEP83, CEP89, CEP164, SCTL1, and FBF-1) and the effector protein associated with CEP164, Tau Tubulin Kinase 2 (TTBK2). While originally studied in relation to Alzheimer's disease, it is now establised that TTBK2 is absolutelly esential for ciliogenesis - no cilia are formed in cells devoid of the active kinase.

The requirement of components of distal appendages for regulation of cilia formation is now well documented. However, how exactly they do it - what molecular events they employ and control, is far less clear. To put the individual pieces of puzzle together to understad How does it work ? is one of the main tasks that keeps us busy.

Because primary cilium uses the mother centriole as basal body, this centriole cannot participate in mitotic spindle formation. For this reason, the cell cycle machinery acts as one of the essential elements controlling cilium formation, maintenance, and disassembly.

It seems that primary cilium formation may be also controlled by regulators of cytokinesis. In our recent study we have identified kinesin KIF14, previously showed to regulate cytokinesis, as a novel regulator of primary cilium formation and function. We found it localizes to cilia, its loss leads to cilia shortening, which is linked to aberrant activation of Aurora kinase (AURA). Intriguingly, inhibition of AURA restores the cilia length, but not ciliary signaling in KIF14-depleted cells.

We aim to provide mechanistical explanation for the rather unexpected role of KIF14 in cilia, and to elucidate the extend of cross-talk between ciliogenesis and cytokinesis regulation.

Successful treatment of human diseases calls for better understanding of their origin. Mounting evidence (animal models, patient data) supports the role for cilia and their individual components in the differentiation and development. For example, brain abnormalities are found in patients with mutated TTBK2 and other cilia-related genes.

We want to elucidate causalities between cilia defects and the key processes of embryogenesis. We are using a model of neural in vitro differentiation of human pluripotent stem cells, to assess what specific function might cilia serve at the particular cell commitment stage (undifferentiated cell, progenitor, precursor, fully differentiated cell).