N-Cadherin Promotes Recruitment and Migration of Neural Progenitor Cells from the SVZ Neural Stem Cell Niche into Demyelinated Lesions

Klingener, Michael; Chavali, Manideep; Singh, Jagdeep; McMillan, Nadia; Coomes, Alexandra; Dempsey, Peter J.; Chen, Emily I.; Aguirre, Adán

doi:10.1523/jneurosci.3699-13.2014

Cited by 41 publications

(33 citation statements)

References 77 publications

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“…However, these cells were not positive for MBP and, therefore, it was concluded that they do not contribute to myelination 36 . After cuprizone-induced demyelination, SVZ-derived myelinating oligodendrocytes have been described in subcortical white matter lesions 37 and the corpus callosum 38 , 39 . However, another study in the cuprizone model reported an increased migration of DCX + cells from the SVZ only towards the olfactory bulb, but not to lesion sites 40 .…”

Section: Discussionmentioning

confidence: 99%

DCX+ neuronal progenitors contribute to new oligodendrocytes during remyelination in the hippocampus

Klein

Mrowetz

Kreutzer

et al. 2020

Sci Rep

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A pool of different types of neural progenitor cells resides in the adult hippocampus. Apart from doublecortin-expressing (DCX+) neuronal progenitor cells (NPCs), the hippocampal parenchyma also contains oligodendrocyte precursor cells (OPCs), which can differentiate into myelinating oligodendrocytes. It is not clear yet to what extent the functions of these different progenitor cell types overlap and how plastic these cells are in response to pathological processes. The aim of this study was to investigate whether hippocampal DCX+ NPCs can generate new oligodendrocytes under conditions in which myelin repair is required. For this, the cell fate of DCX-expressing NPCs was analyzed during cuprizone-induced demyelination and subsequent remyelination in two regions of the hippocampal dentate gyrus of DCX-CreERT2/Flox-EGFP transgenic mice. In this DCX reporter model, the number of GFP+ NPCs co-expressing Olig2 and CC1, a combination of markers typically found in mature oligodendrocytes, was significantly increased in the hippocampal DG during remyelination. In contrast, the numbers of GFP+PDGFRα+ cells, as well as their proliferation, were unaffected by de- or remyelination. During remyelination, a higher portion of newly generated BrdU-labeled cells were GFP+ NPCs and there was an increase in new oligodendrocytes derived from these proliferating cells (GFP+Olig2+BrdU+). These results suggest that DCX-expressing NPCs were able to contribute to the generation of mature oligodendrocytes during remyelination in the adult hippocampus.

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Section: Discussionmentioning

confidence: 99%

DCX+ neuronal progenitors contribute to new oligodendrocytes during remyelination in the hippocampus

Klein

Mrowetz

Kreutzer

et al. 2020

Sci Rep

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“…The demyelinating agent (2 µl of 1% Lysolecithin in 0.9% NaCl) was injected unilaterally into the corpus callosum using stereotaxic coordinates of 1.5 mm anterior–posterior; 1 mm mediolateral and 2 mm dorsoventral from Bregma. The needle was kept in place for 5 min to reduce reflux along the needle track 49 , 58 . The day of injection was noted as day 0, and this served as the starting time point for all measurements of DPI.…”

Section: Methodsmentioning

confidence: 99%

“…Proteomics data were obtained from SVZ tissue of chronically demyelinated adult C57/Bl6 mice that was achieved by 0.2% Cuprizone (cyclohexylidenehydrazide; Sigma-Aldrich; fed ad libitum mixed in pelleted chow diet (Teklad)) 58 treatment for 12 weeks. The GO and pathway enrichment analyses of proteomics data from SVZ tissue at the peak of demyelination were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) software and Reactomics Pathway analysis tool followed by the construction of a protein–protein interaction network.…”

Section: Methodsmentioning

confidence: 99%

Non-canonical Wnt signaling regulates neural stem cell quiescence during homeostasis and after demyelination

et al. 2018

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Adult neural stem cells (NSCs) reside in a specialized microenvironment, the subventricular zone (SVZ), which provides them with unique signaling cues to control their basic properties and prevent their exhaustion. While the signaling mechanisms that regulate NSC lineage progression are well characterized, the molecular mechanisms that trigger the activation of quiescent NSCs during homeostasis and tissue repair are still unclear. Here, we uncovered that the NSC quiescent state is maintained by Rho-GTPase Cdc42, a downstream target of non-canonical Wnt signaling. Mechanistically, activation of Cdc42 induces expression of molecules involved in stem cell identity and anchorage to the niche. Strikingly, during a demyelination injury, downregulation of non-canonical Wnt-dependent Cdc42 activity is necessary to promote activation and lineage progression of quiescent NSCs, thereby initiating the process of tissue repair.

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“…37,40,41,94 Furthermore, experiments using N-cadherin gain-and loss-of-function approaches show that these perturb the neuronal differentiation in chick and zebra fish retina, mouse cerebral cortex, zebra fish cerebellum, and mouse ventral midbrain during development. 11,27,34,39,[95][96][97] In adult zebra fish, down-regulation of N-cadherin is a trigger of the differentiation of NPCs during Rostral migration. 85 In addition, it has been reported that N-cadherin regulates neuronal differentiation from induced pluripotent stem cells (iPSCs).…”

Section: Regulation Of Differentiation Of Npcs By N-cadherinmentioning

confidence: 99%

N-cadherin-based adherens junction regulates the maintenance, proliferation, and differentiation of neural progenitor cells during development

Miyamoto

Sakane

Hashimoto

2015

Cell Adhesion & Migration

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This review addresses our current understanding of the regulatory mechanism by which N-cadherin, a classical cadherin, affects neural progenitor cells (NPCs) during development. N-cadherin is responsible for the integrity of adherens junctions (AJs), which develop in the sub-apical region of NPCs in the neural tube and brain cortex. The apical domain, which contains the sub-apical region, is involved in the switching from symmetric proliferative division to asymmetric neurogenic division of NPCs. In addition, Ncadherin-based AJ is deeply involved in the apico-basal polarity of NPCs and the regulation of Wnt-b-catenin, hedgehog (Hh), and Notch signaling. In this review, we discuss the roles of N-cadherin in the maintenance, proliferation, and differentiation of NPCs through components of AJ, b-catenin and aE-catenin.

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N-Cadherin Promotes Recruitment and Migration of Neural Progenitor Cells from the SVZ Neural Stem Cell Niche into Demyelinated Lesions

Cited by 41 publications

References 77 publications

DCX+ neuronal progenitors contribute to new oligodendrocytes during remyelination in the hippocampus

DCX+ neuronal progenitors contribute to new oligodendrocytes during remyelination in the hippocampus

Non-canonical Wnt signaling regulates neural stem cell quiescence during homeostasis and after demyelination

N-cadherin-based adherens junction regulates the maintenance, proliferation, and differentiation of neural progenitor cells during development

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