ArticleJCI insight2020
MT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis, and hydrocephalus.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Screening the composition of tubulin isotypes reveals the most abundant TUBB4B for ciliary polarity in ependymal cells.Journal of molecular cell biology · 2026Article
- From the past to the present: evolving theories in the pathophysiology of normal pressure hydrocephalus.Journal of neurology, neurosurgery, and psychiatry · 2026Review
- Region-specific roles of stress-activated protein kinase MKK7 in the developing and maturing murine brain.Scientific reports · 2025Article
- HDL-bound S1P affects the subventricular niche and early neuropathological features of Alzheimer's disease.Nature communications · 2025Article
- Hydrocephalus: Molecular and Neuroimaging Biomarkers in Diagnosis and Management.Biomedicines · 2025Review
- Review
- Multiciliated ependymal cells: an update on biology and pathology in the adult brain.Acta neuropathologica · 2024Review
- Intraventricular dimethyl sulfoxide (DMSO) induces hydrocephalus in a dose-dependent pattern.Heliyon · 2024Article
- Ependyma in Neurodegenerative Diseases, Radiation-Induced Brain Injury and as a Therapeutic Target for Neurotrophic Factors.Biomolecules · 2023Review
- Roles of Ependymal Cells in the Physiology and Pathology of the Central Nervous System.Aging and disease · 2023Review
- TIMP3 promotes the maintenance of neural stem-progenitor cells in the mouse subventricular zone.Frontiers in neuroscience · 2023Article
- The genetic background of hydrocephalus in a population-based cohort: implication of ciliary involvement.Brain communications · 2023Article
- METTL3-mediated mMolecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Membrane-type I matrix metalloproteinase (MT1-MMP), lipid metabolism, and therapeutic implications.Journal of molecular cell biology · 2021Review
- Dynamic Expression of Membrane Type 1-Matrix Metalloproteinase (Mt1-mmp/Mmp14) in the Mouse Embryo.Cells · 2021Article
- Hydrocephalus in mouse B3glct mutants is likely caused by defects in multiple B3GLCT substrates in ependymal cells and subcommissural organ.Glycobiology · 2021Article
- The regulatory roles of motile cilia in CSF circulation and hydrocephalus.Fluids and barriers of the CNS · 2021Review
- Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood-brain barrier and neurovascular unit.Fluids and barriers of the CNS · 2021Article
- Motile cilia genetics and cell biology: big results from little mice.Cellular and molecular life sciences : CMLS · 2021Review
- ID4 Is Required for Normal Ependymal Cell Development.Frontiers in neuroscience · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hydrocephalus is characterized by abnormal accumulation of cerebrospinal fluid (CSF) in the ventricular cavity. The circulation of CSF in brain ventricles is controlled by the coordinated beating of motile cilia at the surface of ependymal cells (ECs). Here, we show that MT1-MMP is highly expressed in olfactory bulb, rostral migratory stream, and the ventricular system. Mice deficient for membrane-type 1-MMP (MT1-MMP) developed typical phenotypes observed in hydrocephalus, such as dome-shaped skulls, dilated ventricles, corpus callosum agenesis, and astrocyte hypertrophy, during the first 2 weeks of postnatal development. MT1-MMP-deficient mice exhibited reduced and disorganized motile cilia with the impaired maturation of ECs, leading to abnormal CSF flow. Consistent with the defects in motile cilia morphogenesis, the expression of promulticiliogenic genes was significantly decreased, with a concomitant hyperactivation of Notch signaling in the walls of lateral ventricles in Mmp14-/- brains. Inhibition of Notch signaling by γ-secretase inhibitor restored ciliogenesis in Mmp14-/- ECs. Taken together, these data suggest that MT1-MMP is required for ciliogenesis and EC maturation through suppression of Notch signaling during early brain development. Our findings indicate that MT1-MMP is critical for early brain development and loss of MT1-MMP activity gives rise to hydrocephalus.
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