The primary cilium: a signalling centre during vertebrate development

Abstract

Over the past 10 years, primary cilia have been found to be required for hedgehog (Hh) signalling during development and have been implicated in cystic kidney disease and complex inherited disorders called ciliopathies. In early vertebrate embryos, the primary cilium seems to be dedicated to transduction of Hh signals. Proteins required for building cilia, including the anterograde kinesin-2 motor, components of the intraflagellar transport B (IFTB) complex and a subset of basal-body-associated proteins, are required for Hh signalling in mice and zebrafish, and core components of the Hh pathway localize to cilia in a ligand-dependent manner. By contrast, the evidence suggests that other developmental signalling pathways do not depend on cilia. All Hh signalling in embryos, adult stem cells and tumours depends on the primary cilium. Based on the phenotypes of mutants that lack different components of the IFT machinery, regulated trafficking within the cilium determines the level of Hh signalling. The fused (FU) and KIF7 proteins provide links between IFT and cilia and the Hh pathway. FU and COS2 (the homologue of KIF7) are required for Hh signalling in Drosophila melanogaster, whereas in other invertebrates they are required for ciliogenesis. In vertebrates, FU and KIF7 function in both cilia formation and Hh signalling. Planar cell polarity (PCP) pathways can control the position of primary cilia, and mammalian homologues of proteins that function as PCP effectors in D. melanogaster are required for ciliogenesis. These connections between PCP and cilia position may have a role in cilia function in the inner ear and in the kidney.