ArticleMolecular biology of the cell2009
Myosin IXa regulates epithelial differentiation and its deficiency results in hydrocephalus.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- Extrahepatic and Circulating miR-122: Diagnostic Implications and Future Directions.MicroRNA (Shariqah, United Arab Emirates) · 2025Review
- An allosteric inhibitor of RhoGAP class-IX myosins suppresses the metastatic features of cancer cells.Nature communications · 2024Article
- Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models.Journal of neuromuscular diseases · 2023Review
- Assembly of the Non-Canonical Myo9a-RhoGAP and RhoA·GDP Transition State Complex in the Presence of MgFThe protein journal · 2021Article
- The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis.Cancers · 2021Review
- Rho-GTPase Activating Protein myosin MYO9A identified as a novel candidate gene for monogenic focal segmental glomerulosclerosis.Kidney international · 2021Article
- Motor Proteins and Spermatogenesis.Advances in experimental medicine and biology · 2021Review
- MT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis, and hydrocephalus.JCI insight · 2020Article
- Article
- Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.American journal of human genetics · 2019Article
- Nearly complete deletion of BubR1 causes microcephaly through shortened mitosis and massive cell death.Human molecular genetics · 2019Article
- The RhoGAP HUM-7/Myo9 integrates signals to modulate RHO-1/RhoA during embryonic morphogenesis inDevelopment (Cambridge, England) · 2018Article
- RhoGAP domain-containing fusions and PPAPDC1A fusions are recurrent and prognostic in diffuse gastric cancer.Nature communications · 2018Article
- Loss of p73 in ependymal cells during the perinatal period leads to aqueductal stenosis.Scientific reports · 2017Article
- Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice.EMBO molecular medicine · 2017Article
- Article
- Self-organization of actin networks by a monomeric myosin.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome.Brain : a journal of neurology · 2016Article
- Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus.Nature communications · 2016Article
- Myosin IXa Binds AMPAR and Regulates Synaptic Structure, LTP, and Cognitive Function.Frontiers in molecular neuroscience · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The ependymal multiciliated epithelium in the brain restricts the cerebrospinal fluid to the cerebral ventricles and regulates its flow. We report here that mice deficient for myosin IXa (Myo9a), an actin-dependent motor molecule with a Rho GTPase-activating (GAP) domain, develop severe hydrocephalus with stenosis and closure of the ventral caudal 3rd ventricle and the aqueduct. Myo9a is expressed in maturing ependymal epithelial cells, and its absence leads to impaired maturation of ependymal cells. The Myo9a deficiency further resulted in a distorted ependyma due to irregular epithelial cell morphology and altered organization of intercellular junctions. Ependymal cells occasionally delaminated, forming multilayered structures that bridged the CSF-filled ventricular space. Hydrocephalus formation could be significantly attenuated by the inhibition of the Rho-effector Rho-kinase (ROCK). Administration of ROCK-inhibitor restored maturation of ependymal cells, but not the morphological distortions of the ependyma. Similarly, down-regulation of Myo9a by siRNA in Caco-2 adenocarcinoma cells increased Rho-signaling and induced alterations in differentiation, cell morphology, junction assembly, junctional signaling, and gene expression. Our results demonstrate that Myo9a is a critical regulator of Rho-dependent and -independent signaling mechanisms that guide epithelial differentiation. Moreover, Rho-kinases may represent a new target for therapeutic intervention in some forms of hydrocephalus.
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Registered trials
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