A cilium transmitting an extra-cellular signal to the nucleus - Click to enlarge
At the organ level we are interested how cells are able to react to changes in their microenvironment. Recently, thehas emerged as a crucial sensor of growth factors and physiological parameters in body fluids.
With the GLIS family of transcriptional regulators, we have identified molecular players that are involved in transmitting the signal from the cilium to the nucleus allowing e.g. kidney cells to respond to changes in primary urine composition. In particular, we could show that cilia signaling mediated by the transcriptional regulator GLIS2 is essential to maintain kidney architecture, becausein humans and mice result in a nephronophthisis phenotype.
At the moment we are investigating how cilia signal transduction is regulated at the molecular level through post-translational modifications. Understanding cilia signaling in general will have implications for many human ciliopathies that are caused by malfunctioning of this organelle i.e. Bardet-Biedel syndrome which leads to obesity.