Special issue: Cilia and ciliopathies

Cilia are microtubule‐based tiny organelles that protrude from the cell surface. In recent years, emerging evidence has shown that cilia are essential for many biological functions, and their defects result in a wide range of genetic disorders, termed ciliopathies. According to their motile properties, cilia can be classified as motile or primary (immotile) cilia. Motile cilia are essential for the movement of unicellular organisms, including Chlamydomonas, Tetrahymena, Trypanosoma as well as sperm. In metazoans, beating of motile cilia also facilitates fluid flow over epithelial cell surfaces. On the other hand, primary cilia function as cellular antennae that sense extracellular signals and transduce these signals into the cell, thus, regulating development and cellular physiology. To understand the pathogenic mechanisms of ciliopathies, it is of vital importance to learn the basic mechanisms underlying ciliogenesis, including the diversity and structure of cilia, ciliary signaling and other kinds of ciliary functions. This special issue of the Journal of Cellular Physiology focuses on the structure, assembly, and some of the varied functions of cilia. Despite being part of the cell membrane, the composition of the ciliary membrane is strikingly different. For instance, the ciliary membrane is enriched in a large variety of receptors essential for signaling transduction and cell behavior. The review from Dutta and Ray summarizes the composition, modification of ciliary membrane lipid, and discusses the influences of ciliary lipid composition on cilia growth and signaling. Being a specialized cellular antenna, cilia are essential for the transduction of variety of signals, including Hedgehog signaling. The review from Jin et al. (2022) explore the roles of prostaglandin signaling during ciliogenesis and development. Prostaglandin E2 (PGE2) binds its receptor, EP4, on the ciliary membrane and activates downstream cAMP signals to promote ciliogenesis. Jin et al. (2022) outline recent advances in prostaglandin signaling during ciliogenesis, embryonic development and organogenesis. Motile cilia are essential for directional fluid flow as well as sperm motility, and ciliary motility defects are the major cause of the ciliopathy primary ciliary dyskinesia (PCD). Mutations in a large number of genes encoding ciliary dynein arms or their assembly factors have been demonstrated to be causative of PCD. Qiu and Roy summarize recent findings in the cytoplasmic assembly of dynein arms, their transport into cilia via intraflagellar transport and axonemal docking. This review provides us with a better understanding on how cilia motility is regulated by dynein arms. Moreover, the review from Conde and Dean discusses the structural features of the flagellum in the African trypanosome, and the possibilities of targeting flagellar function to cure trypanosome infections. Finally, Maurya uses the Caenorhabditis elegans model to highlight mechanisms that underlie the enormous structural diversity of cilia. This special issue also contains five original research articles reporting studies of ciliary signaling and function in different organisms as well as human patients. Yang et al. (2022) report the role of Hippo signaling during retina development. Removal of YAP1, specifically in the retinal Muller cells, causes extensive late‐onset retinal degeneration, including cone and rod photoreceptors that have the highly specialized connecting cilium. Jin et al. (2022) studied the role of E2f4 during zebrafish intestine and otolith development. E2f4 regulates the expression of ciliary motility genes, thus, contributing to coordinated ciliary motility in the otic vesicles. Interestingly, E2f4 also participates in the differentiation of the intestinal epithelium. Stereocilia are a distinct class of actin‐based cellular protrusions, whose polarity is regulated by a true cilium, the kinocilium. Yan et al. (2022) report the role of BAIAP2L2 in the maintenance of stereocilia in the mouse cochlear hair cells. Cilia disassembly and cell cycle progression is closely related. For example, the centrosomal protein Trichoplein can promote cell progression through disassembly of cilia. Huang et al. (2022) show that deletion of Trichoplein induces G0 arrest in cultured cells. Strikingly, blocking the formation of cilia could not rescue cell cycle arrest, which requires the inhibition of Rb and p53 signaling. This study uncovers new data pertaining to the function of Trichoplein during cell cycle progression. Finally, Qiu et al. report several patients harboring mutations in the TMEM67 gene, a causative gene for human ciliopathies including Meckel‐Gruber and Joubert syndromes. Interestingly, these patients only exhibited high gamma‐glutamyl transpeptidase cholestasis and congenital hepatic fibrosis without typical symptoms of ciliopathies. These data add new information regarding the broad phenotypic spectrum that arises frommutations in TMEM67. We thank all the authors for their insightful contributions, and we hope that this special issue will appeal to researchers investigating fundamental aspects of ciliary biology as well as those engaged in more clinical aspects of how dysfunction of these organelles causes human disease.