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Article: MT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis, and hydrocephalus

TitleMT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis, and hydrocephalus
Authors
Issue Date2020
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at https://insight.jci.org/
Citation
JCI insight, 2020, v. 5 n. 9, p. article no. e132782 How to Cite?
AbstractHydrocephalus 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.
Persistent Identifierhttp://hdl.handle.net/10722/293494
ISSN
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJIANG, Z-
dc.contributor.authorZhou, J-
dc.contributor.authorQin, X-
dc.contributor.authorZhrng, H-
dc.contributor.authorGao, B-
dc.contributor.authorLiu, X-
dc.contributor.authorJin, G-
dc.contributor.authorZhou, Z-
dc.date.accessioned2020-11-23T08:17:35Z-
dc.date.available2020-11-23T08:17:35Z-
dc.date.issued2020-
dc.identifier.citationJCI insight, 2020, v. 5 n. 9, p. article no. e132782-
dc.identifier.issn2379-3708-
dc.identifier.urihttp://hdl.handle.net/10722/293494-
dc.description.abstractHydrocephalus 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.-
dc.languageeng-
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at https://insight.jci.org/-
dc.relation.ispartofJCI insight-
dc.titleMT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis, and hydrocephalus-
dc.typeArticle-
dc.identifier.emailGao, B: gaobo@hku.hk-
dc.identifier.emailZhou, Z: zhongjun@hku.hk-
dc.identifier.authorityGao, B=rp02012-
dc.identifier.authorityZhou, Z=rp00503-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1172/jci.insight.132782-
dc.identifier.pmid32229724-
dc.identifier.pmcidPMC7253023-
dc.identifier.scopuseid_2-s2.0-85084379350-
dc.identifier.hkuros319252-
dc.identifier.volume5-
dc.identifier.issue9-
dc.identifier.spagearticle no. e132782-
dc.identifier.epagearticle no. e132782-
dc.identifier.isiWOS:000531472400006-
dc.publisher.placeUnited States-
dc.identifier.issnl2379-3708-

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