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| Open AccessHedgehog signaling via its ligand DHH acts as cell fate determinant during skeletal muscle regeneration
Successful skeletal muscle regeneration relies on the interplay of multiple cell populations. Here, the authors describe how ciliary Hedgehog signaling coordinates the intercellular crosstalk required to balance wound healing and fatty fibrosis.
- Alessandra M. Norris
- , Ambili Bai Appu
- & Daniel Kopinke
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| Open AccessSingle-molecule localization microscopy reveals the ultrastructural constitution of distal appendages in expanded mammalian centrioles
The authors have combined direct stochastic optical reconstruction microscopy with expansion microscopy to describe the 3-dimensional molecular organization of centriolar distal appendages.
- Ting-Jui Ben Chang
- , Jimmy Ching-Cheng Hsu
- & T. Tony Yang
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Article
| Open AccessMucociliary Wnt signaling promotes cilia biogenesis and beating
Motile cilia are thought of as signaling-inert nanomotors. Here, the authors show that motile cilia transduce a Wnt-protein phosphatase 1 signal that regulates cilia biogenesis and ciliary beating in Xenopus embryos and in human airway epithelia.
- Carina Seidl
- , Fabio Da Silva
- & Christof Niehrs
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| Open AccessRepair of airway epithelia requires metabolic rewiring towards fatty acid oxidation
Airway epithelial repair, a key process in the recovery from lung injury, requires a metabolic shift from glycolysis to fatty acid oxidation (FAO). Pharmacological FAO promotion enhances epithelial differentiation, suggesting new therapeutic options.
- Stefania Crotta
- , Matteo Villa
- & Andreas Wack
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| Open AccessMicroridge-like structures anchor motile cilia
Motile cilia beat in a defined direction to orchestrate developmental programs, but also to execute janitorial tasks such as clearing airways. Here they show that motile cilia of the Xenopus epidermis are anchored to microridge-like membrane protrusions to maintain their directionality.
- Takayuki Yasunaga
- , Johannes Wiegel
- & Gerd Walz
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| Open AccessWdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules
Ciliary beating is mediated by the axonemal central pair microtubules, though how these non-centrosomal microtubules form is poorly understood. Here the authors show that a trio of proteins act cooperatively to initiate central microtubule formation in mammals.
- Hao Liu
- , Jianqun Zheng
- & Xiumin Yan
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Article
| Open AccessBardet-Biedl syndrome proteins modulate the release of bioactive extracellular vesicles
Extracellular vesicles (EV) are known to be released from the primary cilium, but the role ciliary proteins play in EV biogenesis remains unexplored. Here, the authors demonstrate increased secretion of small EVs with altered cargo composition from cells with known ciliarelated mutations. Wnt related molecules made up a majority of altered cargo
- Ann-Kathrin Volz
- , Alina Frei
- & Helen L. May-Simera
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| Open AccessSiah2 integrates mitogenic and extracellular matrix signals linking neuronal progenitor ciliogenesis with germinal zone occupancy
In neural development, progenitors transition from a proliferative to a differentiated state. Here, the authors show that cerebellar granule neurons retract primary cilia as they exit their proliferative niche upon decreased ECM engagement, enabling radial migration due to loss of Shh sensitivity.
- Taren Ong
- , Niraj Trivedi
- & David J. Solecki
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Article
| Open AccessTALPID3 and ANKRD26 selectively orchestrate FBF1 localization and cilia gating
Most cells possess sensory cilia, which need to be gated properly. Here the authors show that the C. elegans proteins TALP-3 and ANKR-26 coordinate cilia gating in the context of transition fibers and that this mechanism is conserved in mammalian cells and likely implicated in certain ciliopathies.
- Hao Yan
- , Chuan Chen
- & Qing Wei
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Article
| Open AccessWnt-PLC-IP3-Connexin-Ca2+ axis maintains ependymal motile cilia in zebrafish spinal cord
Ependymal cells are supporting cells in the central nervous system. Here the authors elucidate a signalling axis in zebrafish spinal cord ependymal cells that is important for motile cilia assembly and maintenance, demonstrating that it depends on intercellular propagation of calcium ions via connexin 43.
- Jun Zhang
- , Gopalakrishnan Chandrasekaran
- & Seok-Yong Choi
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Article
| Open AccessCiliary exclusion of Polycystin-2 promotes kidney cystogenesis in an autosomal dominant polycystic kidney disease model
The molecular role of ciliary Polycystin-2 (PC2) in cyst formation and polycystic kidney disease (ADKPD) is unclear. Here, the authors identify a PC2 mutant lacking ciliary localisation but with active Ca2+ channel function in mice, that is sufficient to generate an ADPKD phenotype.
- Rebecca V. Walker
- , Jennifer L. Keynton
- & Dominic P. Norris
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Article
| Open AccessPrimary cilia regulate hematopoietic stem and progenitor cell specification through Notch signaling in zebrafish
Haematopoietic stem and progenitor cells (HSPCs) produce all blood lineages and arise from the haemogenic endothelium (HE) during embryogenesis. Here the authors show that genes specific to cilia formation are required for HSPC development in the HE in zebrafish through transduction of Notch signal.
- Zhibin Liu
- , Haiqing Tu
- & Feng Liu
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Article
| Open AccessSecreted metalloproteases ADAMTS9 and ADAMTS20 have a non-canonical role in ciliary vesicle growth during ciliogenesis
Ciliogenesis is a complex process requiring hundreds of molecules, although few secreted proteins have been implicated. Here, the authors show that the secreted metalloproteases ADAMTS9 and ADAMTS20 intracellularly regulate ciliogenesis from unique periciliary vesicles with proteolytic activity.
- Sumeda Nandadasa
- , Caroline M. Kraft
- & Suneel S. Apte
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| Open AccessMicrotubule asters anchored by FSD1 control axoneme assembly and ciliogenesis
Microtubule asters originate from centrosomes but their role during interphase remains largely unknown. Here, the authors find that microtubule asters anchored by previously-uncharacterized FSD1 play a role in ciliogenesis by maintaining the dynamic localization of centriolar satellites.
- Hai-Qing Tu
- , Xuan-He Qin
- & Hui-Yan Li
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| Open AccessAxoneme polyglutamylation regulated by Joubert syndrome protein ARL13B controls ciliary targeting of signaling molecules
The small GTPase ARL13B is mutated in the human ciliopathy Joubert syndrome. Here the authors show that ARL13B and the RAB11 effector FIP5 promote import of tubulin glutamylase into cilia and as such axoneme polyglutamylation, which is demonstrated to be required for cilia signaling.
- Kai He
- , Xiaoyu Ma
- & Jinghua Hu
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Article
| Open AccessSuper-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components
Distal appendages (DAPs) at the cilia base mediate membrane docking during ciliogenesis. Here the authors use super-resolution microscopy to map 16 centriole distal end components, revealing the structure of the backbone of the DAP, as well as a previously undescribed distal appendage matrix.
- T. Tony Yang
- , Weng Man Chong
- & Jung-Chi Liao
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| Open AccessUncovering inherent cellular plasticity of multiciliated ependyma leading to ventricular wall transformation and hydrocephalus
Multiciliated ependymal cells (ECs) in the mammalian brain are glial cells facilitating cerebral spinal fluid movement. This study describes an inherent cellular plasticity of ECs as maintained by Foxj1 and IKK2 signaling, and shows resulting hydrocephalus when EC de-differentiation is triggered.
- Khadar Abdi
- , Chun-Hsiang Lai
- & Chay T. Kuo
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| Open AccessCytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis
Multiciliogenesis requires activation of transcriptional and protein assembly programs; however, the mechanisms that initiate the formation of these multiprotein complexes are unclear. Here the authors show that after inducing centriole biogenesis genes, the transcription factor E2f4 is required in the cytoplasm for assembly and nucleation of deuterosomes.
- Munemasa Mori
- , Renin Hazan
- & Wellington V. Cardoso
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| Open AccessBi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories
Ependymal cells lining the adult brain ventricles are comprised of multiciliated cells and a rare subpopulation with two cilia (E2 cells) whose origin and function remain unknown. Here the authors find E2 cells in the 3rd ventricle of mice and humans, along with a third ependymal cell type with only a primary cilium, and provide details of their marker profile and developmental origins.
- Zaman Mirzadeh
- , Yael Kusne
- & Arturo Alvarez-Buylla
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| Open AccessA mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi
VPS15 is known as a VPS34-associated protein that functions in intracellular trafficking and autophagy. Here the authors identify a role for VPS15 in ciliopathy and ciliary phenotypes, and show that it interacts with GM130 and functions in IFT20-dependent cis-Golgi to cilium trafficking.
- Corinne Stoetzel
- , Séverine Bär
- & Hélène Dollfus
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| Open AccessSevere NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages
Human mutations in the NDE1 gene have been associated with cortical malformations and severe microcephaly. Here, the authors show in embryonic rat brains that NDE1-depleted neural progenitors arrest at three specific cell cycle stages before mitosis, resulting in a severe decrease in neurogenesis.
- David J. Doobin
- , Shahrnaz Kemal
- & Richard B. Vallee
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| Open AccessThe hydrolethalus syndrome protein HYLS-1 regulates formation of the ciliary gate
Transition fibres (TFs) and the transition zone (TZ) are basal ciliary structures thought to act as a gate to regulate protein transport. Here the authors show that the C. elegansorthologue of hydrolethalus protein 1, HYLS-1, disrupts both structures and compromises the trafficking of cargo through the ciliary gate.
- Qing Wei
- , Yingyi Zhang
- & Jinghua Hu
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| Open AccessPhosphatidylinositol phosphate kinase PIPKIγ and phosphatase INPP5E coordinate initiation of ciliogenesis
The primary cilium is essential for embryonic development and tissue pattern formation. Here the authors show that PIPKIγ localizes to the basal body of the primary cilium and cooperates with the Joubert Syndrome associated protein INPP5E to regulate the initiation of ciliogenesis.
- Qingwen Xu
- , Yuxia Zhang
- & Kun Ling
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| Open AccessmiR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways
MicroRNAs of the miR-34/449 family initiate formation of multiciliated cells through the suppression of cell cycle genes and Notch. Here the authors show that miR-34/449 also regulate the assembly of an apical actin network necessary for basal body anchoring by regulating the expression of R-Ras.
- Benoît Chevalier
- , Anna Adamiok
- & Brice Marcet
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| Open AccessDevelopmental disruptions underlying brain abnormalities in ciliopathies
Primary cilia are essential conveyors of signals underlying major cellular functions but their role in brain development is not completely understood. Here the authors compiled a shRNA library targeting ciliopathy genes known to cause brain disorders, and used it to query how ciliopathy genes affect distinct stages of mouse cortical development.
- Jiami Guo
- , Holden Higginbotham
- & E.S. Anton
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Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and vesicle trafficking
Destabilizing the actin cytoskeleton induces the formation of primary cilia, but the mechanism is unknown. Here, Kim et al.show that activity of the transcriptional coactivators YAP/TAZ is regulated by actin remodelling factors, and YAP/TAZ activity correlates with ciliogenesis.
- Jongshin Kim
- , Haiin Jo
- & Joon Kim
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ERK7 regulates ciliogenesis by phosphorylating the actin regulator CapZIP in cooperation with Dishevelled
The actin regulator CapZIP has been shown to regulate ciliogenesis in a phosphorylation-dependent manner. Miyatake et al.show that the atypical MAP kinase ERK7 promotes ciliogenesis by phophorylating CapZIP, and that interactions between both proteins and Dishevelled are required for CapZIP phosphorylation.
- Koichi Miyatake
- , Morioh Kusakabe
- & Eisuke Nishida
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The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis
Although much is known about the structural and trafficking molecules involved in generation of primary cilia, the signalling proteins that regulate ciliogenesis are poorly defined. Here, Kim et al. identify the MST1/2-SAV1 complex, a core component of the Hippo pathway, as a key regulator of ciliogenesis in cells and zebrafish.
- Miju Kim
- , Minchul Kim
- & Dae-Sik Lim
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| Open AccessUbiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension
Biogenesis of the primary cilium begins after cell cycle exit, but the regulatory steps for its formation are poorly defined. Here the authors show that proteasome-mediated removal of the ciliogenesis inhibitor, trichoplein, from mother centrioles initiates the first step of ciliogenesis.
- Kousuke Kasahara
- , Yoshitaka Kawakami
- & Masaki Inagaki
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The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells
Mutations in the deubiquitinase gene CYLD are associated with cylindromatosis, a disease characterized by the development of skin appendage tumours. Eguether et al.discover that CYLD localizes to centrosomes and is required for basal body migration and docking, providing insight into its tumour suppressor activity.
- Thibaut Eguether
- , Maria A. Ermolaeva
- & Anne-Marie Tassin
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Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis
Mutations in the centrosome-cilia gene, Cc2d2a, result in Meckel and Joubert syndromes in humans. By creating Cc2d2a-mutant mice, Veleri et al.show that this gene encodes a component of subdistal appendages; ciliary structures thought to be required to anchor cilia to the microtubule network.
- Shobi Veleri
- , Souparnika H. Manjunath
- & Anand Swaroop