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ADAM10 Regulates NSC Properties Via JAM-C/Rap1 Axis

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dc.contributor.advisor Aguirre, Adan. en_US
dc.contributor.author McMillan, Nadia
dc.contributor.other Department of Neuroscience. en_US
dc.date.accessioned 2018-07-09T13:56:16Z
dc.date.available 2018-07-09T13:56:16Z
dc.date.issued 2017-08-01
dc.identifier McMillan_grad.sunysb_0771E_13222.pdf en_US
dc.identifier.uri http://hdl.handle.net/11401/78350
dc.description 144 pg. en_US
dc.description.abstract In the adult brain, the microenvironment that supports neural stem cell (NSC) properties is known as the subventricular zone (SVZ). The SVZ is organized into an apical compartment adjacent to the ventricular wall and a basal compartment containing a rich vascular network. In this context, quiescent NSCs are arranged at the ventricular wall, while mitotically activated NSCs are found near the basal, vascular region of the SVZ. Expression of extracellular and secreted niche elements are dynamic and tightly controlled to maintain NSC properties, and appear to correlate with NSC positioning within the niche to direct cell intrinsic programs. Despite identification of factors that govern NSC-niche interactions, the signaling mechanisms that regulate NSC positioning to maintain their properties within these niches are still not well defined. In this study, we found a novel role for the protease ‘A disintegrin and metalloproteinase 10’ (ADAM10) in the regulation of NSC anchorage to the ventricular wall and NSC lineage progression. Inhibition of ADAM10 maintains the undifferentiated state of NSCs in the adult SVZ by increasing NSC anchorage to the apical domain. We identified the junctional adhesion molecule C (JAM-C), an apical stem cell marker, as a substrate for ADAM10 in NSCs. Processing of JAM-C by ADAM10 regulates Rap1 activity and this molecular machinery promotes NSC translocation from the apical to the basal compartment and subsequent lineage progression of NSCs. Taken together, our data suggests that ADAM10 activity mediates a pathway essential to the regulation of NSC anchorage to the SVZ ventricular wall and maintains their properties in the adult brain upstream of a signaling paradigm involving JAM-C and Rap1. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.format.mimetype Application/PDF en_US
dc.language.iso en_US en_US
dc.subject.lcsh Neurosciences en_US
dc.subject.lcsh Cytology en_US
dc.subject.other ADAM10 en_US
dc.subject.other cleavage en_US
dc.subject.other neural stem cells en_US
dc.subject.other Rap1 en_US
dc.subject.other subventricular zone en_US
dc.subject.other translocation en_US
dc.title ADAM10 Regulates NSC Properties Via JAM-C/Rap1 Axis en_US
dc.type Dissertation en_US
dc.contributor.committeemember Levine, Joel M. en_US
dc.contributor.committeemember Tsirka, Styliani-Anna E. en_US
dc.contributor.committeemember Goldman, James E. en_US

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