N-cadherin promotes recruitment and migration of neural progenitor cells from the SVZ neural stem cell niche into demyelinated lesions.

[wiskott-aldrich syndrome]

Discrete cellular microenvironments regulate stem cell pools and their development , as well as function in maintaining tissue homeostasis . Although the signaling elements modulating neural progenitor cells (NPCs ) of the adult subventricular zone (SVZ ) niche are fairly well understood , the pathways activated following injury and the resulting outcomes , are less clear . In the present study , we used mouse models of demyelination and proteomics analysis to identify molecular cues present in the adult SVZ niche during injury , and analyzed their role on NPCs in the context of promoting myelin repair . Proteomic analysis of SVZ tissue from mice with experimental demyelination identified several proteins that are known to play roles in NPC proliferation , adhesion , and migration . Among the proteins found to be upregulated were members of the N-cadherin signaling pathway . During the onset of demyelination in the subcortical white matter (SCWM ), activation of epidermal growth factor receptor (EGFR ) signaling in SVZ NPCs stimulates the interaction between N-cadherin and ADAM 10 . Upon cleavage and activation of N-cadherin signaling by ADAM 10 , NPCs undergo cytoskeletal rearrangement and polarization , leading to enhanced migration out of the SVZ into demyelinated lesions of the SCWM . Genetically disrupting either EGFR signaling or ADAM 10 inhibits this pathway , preventing N-cadherin regulated NPC polarization and migration . Additionally , in vivo experiments using N-cadherin gain- and loss -of-function approaches demonstrated that N-cadherin enhances the recruitment of SVZ NPCs into demyelinated lesions . Our data revealed that EGFR -dependent N-cadherin signaling physically initiated by ADAM 10 cleavage is the response of the SVZ niche to promote repair of the injured brain .

Diseases
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Diseases presenting "enhanced migration out of the svz into demyelinated lesions of the scwm" symptom

wiskott-aldrich syndrome

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