Cilia-Based New Discoveries: Ciliogenesis, Function, and Human Diseases

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 31 January 2025 | Viewed by 624

Special Issue Editor


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Guest Editor
Applied Human Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University, Rigshospitalet, Glostrup, Denmark
Interests: primary cilia; Bardet–Biedl syndrome; RPE; iPSC; RT-PCR; movement disorder; tuberous sclerosis
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Special Issue Information

Dear Colleagues,

The interest in the primary cilia has drastically increased since it was first described in 1898. The number of diseases where the primary cilia seem to play an important role is constantly increasing. Primary cilia are non-motile antenna-like structures present in a single copy on the surface of most growth-arrested mammalian cells, including stem cells, neurons, and astrocytes. The primary cilium coordinates a series of signal transduction pathways, including Hedgehog, PDGFRalpha, WNT, mTOR, and integrin signaling. Defects in the primary cilium have been associated with a large number of phenotypes, including developmental defects, kidney diseases, cancer, tuberous sclerosis, Bardet–Biedl syndrome, obesity, and diabetes. However, much remains to be carried out before we have a full understanding of the function of this organelle. Increased knowledge could lead to the identification of new drug targets.

The aim of this Special Issue is to focus on new insights into the role of the primary cilium with relevance to human disease.

Dr. Lisbeth Birk Møller
Guest Editor

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Keywords

  • primary cilium
  • human disease
  • cell signaling
  • mTOR
  • Hedgehog
  • WNT
  • PDGFRalpha

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Published Papers (1 paper)

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Research

19 pages, 7505 KiB  
Article
Loss of Dnah5 Downregulates Dync1h1 Expression, Causing Cortical Development Disorders and Congenital Hydrocephalus
by Koichiro Sakamoto, Masakazu Miyajima, Madoka Nakajima, Ikuko Ogino, Kou Horikoshi, Ryo Miyahara, Kaito Kawamura, Kostadin Karagiozov, Chihiro Kamohara, Eri Nakamura, Nobuhiro Tada and Akihide Kondo
Cells 2024, 13(22), 1882; https://doi.org/10.3390/cells13221882 - 14 Nov 2024
Viewed by 354
Abstract
Dnah5 is associated with primary ciliary dyskinesia in humans. Dnah5-knockout (Dnah5−/− mice develop acute hydrocephalus shortly after birth owing to impaired ciliary motility and cerebrospinal fluid (CSF) stagnation. In contrast to chronic adult-onset hydrocephalus observed in other models, this rapid [...] Read more.
Dnah5 is associated with primary ciliary dyskinesia in humans. Dnah5-knockout (Dnah5−/− mice develop acute hydrocephalus shortly after birth owing to impaired ciliary motility and cerebrospinal fluid (CSF) stagnation. In contrast to chronic adult-onset hydrocephalus observed in other models, this rapid ventricular enlargement indicates additional factors beyond CSF stagnation. Herein, we investigated the contributors to rapid ventricular enlargement in congenital hydrocephalus. Dnah5−/− mice were generated using CRISPR/Cas9. The expression of dynein, N-cadherin, and nestin in the cerebral cortex was assessed using microarrays and immunostaining. Real-time PCR and Western blotting were performed for gene and protein quantification, respectively. All Dnah5−/− mice developed hydrocephalus, confirmed by electron microscopy, indicating the absence of axonemal outer dynein arms. Ventricular enlargement occurred rapidly, with a 25% reduction in the number of mature neurons in the motor cortex. Dync1h1 expression was decreased, while cytoplasmic dynein levels were 56.3% lower. Levels of nestin and N-cadherin in the lateral ventricular walls decreased by 31.7% and 33.3%, respectively. Reduced cytoplasmic dynein disrupts neurogenesis and axonal growth and reduces neuron cortical density. Hydrocephalus in Dnah5−/− mice may result from cortical maldevelopment due to cytoplasmic dynein deficiency, further exacerbating ventricular enlargement due to CSF stagnation caused by impaired motile ciliary function. Full article
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