Mutations in Hydin impair ciliary motility in mice

Chlamydomonas reinhardtii hydin is a central pair protein required for flagellar motility, and mice with Hydin defects develop lethal hydrocephalus. To determine if defects in Hydin cause hydrocephalus through a mechanism involving cilia, we compared the morphology, ultrastructure, and activity of cilia in wild-type and hydin mutant mice strains. The length and density of cilia in the brains of mutant animals is normal. The ciliary axoneme is normal with respect to the 9 + 2 microtubules, dynein arms, and radial spokes but one of the two central microtubules lacks a specific projection. The hydin mutant cilia are unable to bend normally, ciliary beat frequency is reduced, and the cilia tend to stall. As a result, these cilia are incapable of generating fluid flow. Similar defects are observed for cilia in trachea. We conclude that hydrocephalus in hydin mutants is caused by a central pair defect impairing ciliary motility and fluid transport in the brain.

• Publication year

  2008

• Venue

  Journal of Cell Biology

• Publication date

  2008-02-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200710162PMID 18250199PMCID 2234243
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• When cilia go bad: cilia defects and ciliopathies

  2008cited by this paper
• The hydrocephalus inducing gene product, Hydin, positions axonemal central pair microtubules

  2007cited by this paper
• Chlamydomonas reinhardtii hydin is a central pair protein required for flagellar motility

  2007cited by this paper
• Altered pHi regulation and Na+/HCO3− transporter activity in choroid plexus of cilia-defective Tg737orpk mutant mouse

  2007cited by this paper
• A positive feedback mechanism governs the polarity and motion of motile cilia

  2007cited by this paper
• Altered pH(i) regulation and Na(+)/HCO3(-) transporter activity in choroid plexus of cilia-defective Tg737(orpk) mutant mouse.

  2007cited by this paper
• When cilia go bad: cilia defects and ciliopathies

  2007cited by this paper
• Accelerated mortality from hydrocephalus and pneumonia in mice with a combined deficiency of SPAG6 and SPAG16L reveals a functional interrelationship between the two central apparatus proteins.

  2007cited by this paper
• The graded response to Sonic Hedgehog depends on cilia architecture.

  2007cited by this paper
• Flagellar motility is required for the viability of the bloodstream trypanosome

  2006cited by this paper
• Three types of cilia including a novel 9+4 axoneme on the notochordal plate of the rabbit embryo

  2006cited by this paper
• A 360-kb interchromosomal duplication of the human HYDIN locus.

  2006influential reference
• The ciliopathies: an emerging class of human genetic disorders.

  2006cited by this paper
• Ciliary beat frequency is maintained at a maximal rate in the small airways of mouse lung slices.

  2006cited by this paper
• Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination.

  2005cited by this paper
• Proteomic analysis of a eukaryotic cilium

  2005cited by this paper
• Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus

  2005cited by this paper
• Primary Ciliary Dyskinesia: A Review

  2005cited by this paper
• Primary ciliary dyskinesia: Clinical presentation, diagnosis and genetics

  2005cited by this paper
• Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene.

  2004cited by this paper
• Absent inner dynein arms in a fetus with familial hydrocephalus‐situs abnormality

  2004cited by this paper
• Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation.

  2004cited by this paper
• The radial spokes and central apparatus: mechano-chemical transducers that regulate flagellar motility.

  2004cited by this paper
• Central microtubular agenesis causing primary ciliary dyskinesia.

  2004cited by this paper
• Primary ciliary dyskinesia: diagnostic and phenotypic features.

  2004cited by this paper
• Analysis of microtubule sliding patterns in Chlamydomonas flagellar axonemes reveals dynein activity on specific doublet microtubules

  2004cited by this paper
• Speculations on the evolution of 9+2 organelles and the role of central pair microtubules

  2004cited by this paper
• Bend propagation drives central pair rotation in Chlamydomonas reinhardtii flagella

  2004cited by this paper
• Orientation of the central pair complex during flagellar bend formation in Chlamydomonas.

  2003cited by this paper
• Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia☆

  2003influential reference
• Central-pair-linked regulation of microtubule sliding by calcium in flagellar axonemes

  2003cited by this paper
• Congenital hydrocephalus in hy3 mice is caused by a frameshift mutation in Hydin, a large novel gene.

  2003influential reference
• Oscillations in ciliary beat frequency and intracellular calcium concentration in rabbit tracheal epithelial cells induced by ATP

  2003cited by this paper
• Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus.

  2002cited by this paper
• Genetic mapping of an insertional hydrocephalus-inducing mutation allelic to hy3

  2002cited by this paper
• Male Infertility, Impaired Sperm Motility, and Hydrocephalus in Mice Deficient in Sperm-Associated Antigen 6

  2002influential reference
• Regulation of flagellar dynein by the axonemal central apparatus.

  2002cited by this paper
• Ciliary dyskinesia associated with hydrocephalus and mental retardation in a Jordanian family.

  2001cited by this paper
• Abnormal central complex is a marker of severity in the presence of partial ciliary defect.

  2001cited by this paper
• Chlamydomonas IFT88 and Its Mouse Homologue, Polycystic Kidney Disease Gene Tg737, Are Required for Assembly of Cilia and Flagella

  2000cited by this paper
• Primary ciliary dyskinesia (PCD)

  2000cited by this paper
• Asymmetry of cilia and of mice and men.

  1999cited by this paper
• Characterization of a Chlamydomonas Insertional Mutant that Disrupts Flagellar Central Pair Microtubule-associated Structures

  1999cited by this paper
• Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein.

  1998cited by this paper
• The role of central apparatus components in flagellar motility and microtubule assembly.

  1997cited by this paper
• Communicating hydrocephalus in dogs with congenital ciliary dysfunction.

  1995cited by this paper
• Ultrastructure of respiratory cilia of WIC-Hyd male rats. An animal model for human immotile cilia syndrome.

  1991cited by this paper
• Re‐evaluation of GM2346 from a del(16)(q22) to t(4;16)(q35;q22.1)

  1990cited by this paper
• Hydrocephalus, bronchiectasis, and ciliary aplasia.

  1990cited by this paper
• Splitting the ciliary axoneme: implications for a "switch-point" model of dynein arm activity in ciliary motion.

  1989cited by this paper
• Genetic dissection of the central pair microtubules of the flagella of Chlamydomonas reinhardtii

  1984cited by this paper
• Genetic Disorders of Cilia

  1981cited by this paper
• Cilia with defective radial spokes: a cause of human respiratory disease.

  1979cited by this paper
• Chlamydomonas flagellar mutants lacking radial spokes and central tubules. Structure, composition, and function of specific axonemal components

  1978cited by this paper
• Observations of the structural components of flagellar axonemes and central pair microtubules from rat sperm.

  1977cited by this paper
• Pathogenesis of aqueductal occlusion in congenital murine hydrocephalus.

  1976cited by this paper
• Subsidiary components of the flagella of Chlamydomonas reinhardii.

  1970cited by this paper
• THE RELATIONSHIP BETWEEN THE FINE STRUCTURE AND DIRECTION OF BEAT IN GILL CILIA OF A LAMELLIBRANCH MOLLUSC

  1961cited by this paper
• Two new mutant genes in the house mouse

  1943cited by this paper

• Distinct Phenotypes of Primary Ciliary Dyskinesia in Monozygotic Twins with Defective HYDIN Gene: a Case Report

  2026cites this paper
• Domain-Level Interaction of FAP174 (MYCBP-1) and FAP147 (MYCBPAP) Proteins of the C2a Projection of Chlamydomonas Cilia.

  2026cites this paper
• ASH: a new protein domain on the horizon

  2025cites this paper
• Exon Skipping Therapy Restores Ciliary Function in USH2A-Related Retinal Degeneration

  2025cites this paper
• Genetic and molecular mechanisms of hydrocephalus

  2025cites this paper
• Ccdc13 is essential for the assembly of ciliary central microtubules.

  2025cites this paper
• Dynamics and emergence of metachronal waves in the ciliary band of a metazoan larva

  2025cites this paper
• Cytosolic Carboxypeptidase 5 maintains mammalian ependymal multicilia to ensure proper homeostasis and functions of the brain

  2025cites this paper
• In situ structure of the mouse sperm central apparatus reveals mechanistic insights into asthenozoospermia

  2025cites this paper
• Hypersensitivity to type I interferon as a cause of hydrocephalus development.

  2024cites this paper
• Development of functional spermatozoa in mammalian spermiogenesis.

  2024cites this paper
• Isolation of ependymal cilia from mouse brain.

  2024cites this paper
• GDF15 controls primary cilia morphology and function thereby affecting progenitor proliferation

  2024cites this paper
• A polarized multicomponent foundation upholds ciliary central microtubules

  2024cites this paper
• Hydin as the Candidate Master Sex Determination Gene in Channel Catfish (Ictalurus punctatus) and Its Epigenetic Regulation

  2024cites this paper
• BBS genes are involved in accelerated proliferation and early differentiation of BBS-related tissues.

  2024cites this paper
• Multiciliated ependymal cells: an update on biology and pathology in the adult brain

  2024cites this paper
• Combined approaches, including long-read sequencing, address the diagnostic challenge of HYDIN in primary ciliary dyskinesia

  2024cites this paper
• Distinct roles of Kif6 and Kif9 in mammalian ciliary trafficking and motility

  2024cites this paper
• CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

  2024cites this paper
• Localisation and function of key axonemal microtubule inner proteins and dynein docking complex members reveal extensive diversity among vertebrate motile cilia.

  2024cites this paper
• Biomechanical instability of the brain-CSF interface in hydrocephalus.

  2024cites this paper
• Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China

  2024cites this paper
• Motile Cilia in Female and Male Reproductive Tracts and Fertility

  2024cites this paper
• In-cell structural insight into the asymmetric assembly of central apparatus in mammalian sperm axoneme

  2024cites this paper
• HYDIN mutation status as a potential predictor of immune checkpoint inhibitor efficacy in melanoma

  2023cites this paper
• Schmidtea mediterranea as a Model Organism to Study the Molecular Background of Human Motile Ciliopathies

  2023cites this paper
• Roles of Ependymal Cells in the Physiology and Pathology of the Central Nervous System

  2023cites this paper
• Outcomes of the 2019 hydrocephalus association workshop, "Driving common pathways: extending insights from posthemorrhagic hydrocephalus"

  2023cites this paper
• Analysis of motility and mucociliary function of tracheal epithelial cilia.

  2023cites this paper
• Biomechanical effects of hyper-dynamic cerebrospinal fluid flow through the cerebral aqueduct in idiopathic normal pressure hydrocephalus patients.

  2023cites this paper
• The putative protein kinase Stk36 is essential for ciliogenesis and CSF flow by associating with Ulk4

  2023cites this paper
• Formation and function of multiciliated cells

  2023influential citation
• Growth/differentiation factor 15 controls primary cilia morphology in the murine ventricular-subventricular zone thereby affecting progenitor proliferation

  2023cites this paper
• Novel HYDIN variants associated with male infertility in two Chinese families

  2023cites this paper
• Genetic and chemical disruption of amyloid precursor protein processing impairs zebrafish sleep maintenance

  2023cites this paper
• Male infertility‐associated Ccdc108 regulates multiciliogenesis via the intraflagellar transport machinery

  2022cites this paper
• Molecular Mechanisms and Risk Factors for the Pathogenesis of Hydrocephalus

  2022cites this paper
• Is IIIG9 a New Protein with Exclusive Ciliary Function? Analysis of Its Potential Role in Cancer and Other Pathologies

  2022cites this paper
• Rethinking the cilia hypothesis of hydrocephalus.

  2022cites this paper
• Ependymal cells and neurodegenerative disease: outcomes of compromised ependymal barrier function

  2022cites this paper
• Refractory neutrophilic asthma and ciliary genes.

  2022cites this paper
• HYDIN Variants Are a Common Cause of Primary Ciliary Dyskinesia in French-Canadians.

  2022cites this paper
• Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries

  2022cites this paper
• A look under the hood of the machine that makes cilia beat

  2022cites this paper
• Genomic imprinting-like monoallelic paternal expression determines sex of channel catfish

  2022cites this paper
• Transforming growth factor-β1 and bone morphogenetic protein-2 inhibit differentiation into mature ependymal multiciliated cells.

  2022cites this paper
• Intertwined Wdr47-NTD dimer recognizes a basic-helical motif in Camsap proteins for proper central-pair microtubule formation.

  2022cites this paper
• Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort

  2022cites this paper
• Title: “Genetic and chemical disruption of Amyloid Precursor Protein processing impairs zebrafish sleep maintenance”

  2022cites this paper
• Correction: A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice

  2021cites this paper
• Amyloid precursor protein localises to ependymal cilia in vertebrates and is required for ciliogenesis and brain development in zebra sh

  2021cites this paper
• The flagellar germ‐line hypothesis: How flagellate and ciliate gametes significantly shaped the evolution of organismal complexity

  2021cites this paper
• IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment

  2021cites this paper
• Tracheal motile cilia in mice require CAMSAP3 for the formation of central microtubule pair and coordinated beating

  2021cites this paper
• Amyloid precursor protein localises to ependymal cilia in vertebrates and is required for ciliogenesis and brain development in zebrafish

  2021cites this paper
• Tracheal motile cilia in mice require CAMSAP3 for formation of central microtubule pair and coordinated beating

  2021cites this paper
• LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice

  2021cites this paper
• Ependymal ciliary motion and their role in congenital hydrocephalus

  2021cites this paper
• Microglia activated by microbial neuraminidase contributes to ependymal cell death

  2021cites this paper
• Central Apparatus, the Molecular Kickstarter of Ciliary and Flagellar Nanomachines

  2021cites this paper
• The localization of amyloid precursor protein to ependymal cilia in vertebrates and its role in ciliogenesis and brain development in zebrafish

  2021cites this paper
• Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia

  2021cites this paper
• The regulatory roles of motile cilia in CSF circulation and hydrocephalus

  2021cites this paper
• Cumulative Damage: Cell Death in Posthemorrhagic Hydrocephalus of Prematurity

  2021cites this paper
• Advance Publication Experimental Animals

  2020cites this paper
• A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice

  2020cites this paper
• A genome-wide association study revealed five SNPs affecting 8-month weight in sheep.

  2020cites this paper
• The multi‐scale architecture of mammalian sperm flagella and implications for ciliary motility

  2020cites this paper
• Bi-allelic variant c.8638_8658dup in HYDIN causes bronchiectasis in two siblings

  2020cites this paper
• Motile cilia genetics and cell biology: big results from little mice

  2020cites this paper
• Cilia density and flow velocity affect alignment of motile cilia from brain cells

  2020cites this paper
• Ependyma

  2020cites this paper
• BBS4 Is Essential for Nuclear Transport of Transcription Factors Mediating Neuronal ER Stress Response

  2020cites this paper
• Complex Genetic Architecture Underlies Regulation of Influenza-A-Virus-Specific Antibody Responses in the Collaborative Cross

  2020cites this paper
• Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules

  2020cites this paper
• A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice

  2020cites this paper
• HYDIN loss-of-function inhibits GATA4 expression and enhances atrial septal defect risk.

  2020cites this paper
• Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing

  2020cites this paper
• Chronic arsenic exposure lowered sperm motility via impairing ultra-microstructure and key proteins expressions of sperm acrosome and flagellum formation during spermiogenesis in male mice.

  2020cites this paper
• MT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis and hydrocephalus.

  2020cites this paper
• BBS4 Is Essential for Nuclear Transport of Transcription Factors Mediating Neuronal ER Stress Response

  2020cites this paper
• The somatic mutation landscape of Chinese Colorectal Cancer

  2020cites this paper
• Analysis of the sperm flagellar axoneme using gene-modified mice

  2020cites this paper
• Testis‐enriched kinesin KIF9 is important for progressive motility in mouse spermatozoa

  2020cites this paper
• Basalin is an evolutionarily unconstrained protein revealed via a conserved role in flagellum basal plate function

  2019cites this paper
• DNA variants are an unlikely explanation for the changing quality of spermatozoa within the same individual

  2019cites this paper
• Anatomy and Physiology of the Ventricular System

  2019cites this paper
• Rare Human Diseases: Model Organisms in Deciphering the Molecular Basis of Primary Ciliary Dyskinesia

  2019cites this paper
• Motile cilia hydrodynamics: Entrainment versus synchronisation when coupling through flow

  2019cites this paper
• Microtubule-bundling protein Spef1 enables mammalian ciliary central apparatus formation

  2019cites this paper
• Live cell imaging of dynamic behaviors of motile cilia and primary cilium.

  2019cites this paper
• LPA1/3 overactivation induces neonatal posthemorrhagic hydrocephalus through ependymal loss and ciliary dysfunction

  2019cites this paper
• 12-17-2014 FAP 206 is a Microtubule-Docking Adapter for Ciliary Radial Spoke 2 and Dynein c

  2019cites this paper
• Ciliary Proteins: Filling the Gaps. Recent Advances in Deciphering the Protein Composition of Motile Ciliary Complexes

  2019cites this paper
• Cell type-specific expression of testis elevated genes based on transcriptomics and antibody-based proteomics.

  2019cites this paper
• Cerebrospinal Fluid Disorders

  2019cites this paper
• Functions of thioredoxin1 in brain development and in response to environmental chemicals in zebrafish embryos.

  2019cites this paper
• Identification and mapping of central pair proteins by proteomic analysis

  2019influential citation
• SPEF2- and HYDIN-mutant Cilia Lack the Central Pair Associated Protein SPEF2 Aiding PCD Diagnostics.

  2019cites this paper