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

Jiang, Zhixin; Zhou, Jin; Xin, Qin; Zheng, Hongchen; Gao, Bo; Liu, Xinguang; Jin, Guoxiang; Zhou, Zhongjun

doi:10.1172/jci.insight.132782

Cited by 23 publications

(26 citation statements)

References 67 publications

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“…Although there is no detailed analysis of MT1-MMP expression, mRNA levels have been detected in the embryonic brain supporting our data [ 20 ]. Recently, LacZ staining was reported in the olfactory bulb, neural progenitors of the ventricular zone, rostral migratory stream and midbrain of postnatal brains [ 27 ]. Indeed, deficient mice for MT1-MMP display several defects in brain development including corpus callosum agenesis, enlarged ventricles and astrocytosis.…”

Section: Resultsmentioning

confidence: 99%

“…Expression of MT1-MMP has been reported in the olfactory bulb and the rostral migratory stream. On the other hand, its loss of function has been recently related to developmental abnormalities in the ventricular system, mainly with fewer and disorganized cilia in the ependymal cells [ 27 ]. Further, hypothalamic expression of MT1-MMP in the arcuate nucleus is required to establish the right neuronal connections in the center for appetite [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Expression of Membrane Type 1-Matrix Metalloproteinase (Mt1-mmp/Mmp14) in the Mouse Embryo

Muñoz-Sáez

Moracho

Learte

et al. 2021

Cells

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MT1-MMP/MMP14 belongs to a subgroup of the matrix metalloproteinases family that presents a transmembrane domain, with a cytosolic tail and the catalytic site exposed to the extracellular space. Deficient mice for this enzyme result in early postnatal death and display severe defects in skeletal, muscle and lung development. By using a transgenic line expressing the LacZ reporter under the control of the endogenous Mt1-mmp promoter, we reported a dynamic spatiotemporal expression pattern for Mt1-mmp from early embryonic to perinatal stages during cardiovascular development and brain formation. Thus, Mt1-mmp shows expression in the endocardium of the heart and the truncus arteriosus by E8.5, and is also strongly detected during vascular system development as well as in endothelial cells. In the brain, LacZ reporter expression was detected in the olfactory bulb, the rostral cerebral cortex and the caudal mesencephalic tectum. LacZ-positive cells were observed in neural progenitors of the spinal cord, neural crest cells and the intersomitic region. In the limb, Mt1-mmp expression was restricted to blood vessels, cartilage primordium and muscles. Detection of the enzyme was confirmed by Western blot and immunohistochemical analysis. We suggest novel functions for this metalloproteinase in angiogenesis, endocardial formation and vascularization during organogenesis. Moreover, Mt1-mmp expression revealed that the enzyme may contribute to heart, muscle and brain throughout development.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dynamic Expression of Membrane Type 1-Matrix Metalloproteinase (Mt1-mmp/Mmp14) in the Mouse Embryo

Muñoz-Sáez

Moracho

Learte

et al. 2021

Cells

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“…Despite higher intensity of ZO-1 staining, we found no notable differences in the number of pinwheels or the number of monociliated cells (corresponding to B1 cells) in the center of the pinwheels ( Figures 3D,E ). Several reports have linked PCP disruption with CSF flow alterations ( Mirzadeh et al, 2010 ; Jiang et al, 2020 ). To investigate whether PCP of ependymal cells could be altered in Id4KO brains, we measured cilia BB orientation ( Mirzadeh et al, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

ID4 Is Required for Normal Ependymal Cell Development

et al. 2021

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Ependymal cells are radial glia-derived multiciliated cells lining the lateral ventricles of the brain and spinal cord. Correct development and coordinated cilia beating is essential for proper cerebrospinal fluid (CSF) flow and neurogenesis modulation. Dysfunctions of ependymal cells were associated with transcription factor deregulation. Here we provide evidence that the transcriptional regulator ID4 is involved in ependymal cell development and maturation. We observed that Id4-deficient mice display altered ventricular cell cytoarchitecture, decreased ependymal cell number and enlarged ventricles. In addition, absence of ID4 during embryonic development resulted in decreased ependymal cell number and delayed maturation. Our findings open the way for a potential role of ID4 in ependymal cell development and motor cilia function.

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“…In addition, evidence suggests that there are further links between MT1-MMP function and the Wnt/PCP signaling pathway through the transmembrane receptor PTK7, which is an essential regulator of both the canonical and non-canonical Wnt pathways, as well as a proteolytic target of MT1-MMP required for redistribution of polarized cell membranes upon cleavage 131 (Table 1). In this regard, a defect in PTK7 cleavage may explain the inappropriate ciliary organization in mouse ependymal cells, where ciliary defects associated to disrupted polarity are shown upon MT1-MMP loss, suggesting that MT1-MMP may be essential for planar polarization of ependymal cells 74 . Furthermore, Wnt signaling pathway may contribute to ensure proper trafficking of MT1-MMP to specific sites for polarized structure formation in several contexts, in a process required to enable distribution between the apical and basal cell surfaces 34,60 .…”

Section: Developmental Dynamicsmentioning

confidence: 99%

Emerging roles ofMT‐MMPsin embryonic development

Moracho

Learte

Muñoz-Sáez

et al. 2021

Developmental Dynamics

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Membrane-type matrix metalloproteinases (MT-MMPs) are cell membrane-tethered proteinases that belong to the family of the MMPs. Apart from their roles in degradation of the extracellular milieu, MT-MMPs are able to activate through proteolytic processing at the cell surface distinct molecules such as receptors, growth factors, cytokines, adhesion molecules and other pericellular proteins. Although most of the information regarding these enzymes comes from cancer studies, our current knowledge about their contribution in distinct developmental processes occurring in the embryo is limited. In this review, we want to summarize the involvement of MT-MMPs in distinct processes during embryonic morphogenesis, including cell migration and proliferation, epithelialmesenchymal transition, cell polarity and branching, axon growth and navigation, synapse formation, and angiogenesis. We also considered information about MT-MMP functions from studies assessed in pathological conditions and compared these data with those relevant for embryonic development.

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

Cited by 23 publications

References 67 publications

Dynamic Expression of Membrane Type 1-Matrix Metalloproteinase (Mt1-mmp/Mmp14) in the Mouse Embryo

Dynamic Expression of Membrane Type 1-Matrix Metalloproteinase (Mt1-mmp/Mmp14) in the Mouse Embryo

ID4 Is Required for Normal Ependymal Cell Development

Emerging roles ofMT‐MMPsin embryonic development

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