| dc.identifier.uri | http://hdl.handle.net/11401/78366 | |
| 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 | |
| dc.format.medium | Electronic Resource | en_US |
| dc.format.mimetype | Application/PDF | en_US |
| dc.language.iso | en_US | |
| dc.type | Dissertation | |
| dcterms.abstract | While the importance of the subventricular zone (SVZ) in brain development and homeostasis has become more well appreciated over the last few decades, many of the mechanisms regulating SVZ development remain unclear. In particular, the role of extracellular matrix (ECM)-mediated signals in shaping the development and function of the postnatal SVZ remain poorly understood, despite the recognized role of ECM in other stem cell niches. We now report that during the first weeks of postnatal development, ECM is reorganized into laminin-rich "hubs" at the interface between neural stem cells and ependymal cells at the ventricular surface. This ECM is of predominantly ependymal cell origin, and the process of hub assembly and organization is regulated by the ECM receptor dystroglycan. Laminin and dystroglycan function in a reciprocal axis wherein dystroglycan, required for appropriate surface laminin assembly, also transmits laminin-mediated signals into the cell. Dystroglycan in the postnatal SVZ helps establish proper niche organization and function. Either genetic removal of dystroglycan or blockade of dystroglycan binding engenders several defects in neural stem cell function in the perinatal SVZ. These include: (i) dysregulation of radial glial proliferation and differentiation, delaying the emergence of progeny ependymal cells that serve as niche support cells in the adult SVZ; (ii) perturbations in ependymal cell polarity and niche organization into pinwheel-like structures; (iii) increased gliogenesis with increases in both the production and proliferation of oligodendrocyte progenitors; and (iv) delayed maturation of oligodendrocyte precursor cells. Furthermore, dystroglycan is identified as a novel regulator of notch signaling, suppressing notch signaling in neural stem cells, ependymal cells, and oligodendrocyte progenitor cells. Finally, we find that dystroglycan appears to play distinct, and at times, opposing roles in neural stem cells and ependymal cells to maintain SVZ neural stem cell homeostasis. In particular, ependymal cell dystroglycan plays both cell-autonomous and non-autonomous roles in regulating SVZ proliferation and the morphology of neural stem cells. These phenotypes occur in spatially distinct domains of the SVZ, highlighting the functional heterogeneity of ECM in the SVZ. | |
| dcterms.available | 2018-07-09T14:26:28Z | |
| dcterms.contributor | Talmage, David | en_US |
| dcterms.contributor | Colognato, Holly. | en_US |
| dcterms.contributor | Takemaru, Ken-Ichi | en_US |
| dcterms.contributor | Choi, Dennis. | en_US |
| dcterms.creator | Sharma, Himanshu | |
| dcterms.dateAccepted | 2018-07-09T14:26:28Z | |
| dcterms.dateSubmitted | 2018-07-09T14:26:28Z | |
| dcterms.description | Department of Molecular and Cellular Pharmacology. | en_US |
| dcterms.extent | 163 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | Sharma_grad.sunysb_0771E_13248.pdf | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/78366 | |
| dcterms.issued | 2017-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Submitted by Jason Torre (fjason.torre@stonybrook.edu) on 2018-07-09T14:26:28Z
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Sharma_grad.sunysb_0771E_13248.pdf: 6941574 bytes, checksum: 567c6d68e766fe223801283d17afaa91 (MD5) | en |
| dcterms.provenance | Made available in DSpace on 2018-07-09T14:26:28Z (GMT). No. of bitstreams: 1
Sharma_grad.sunysb_0771E_13248.pdf: 6941574 bytes, checksum: 567c6d68e766fe223801283d17afaa91 (MD5)
Previous issue date: 2017-08-01 | en |
| dcterms.subject | Dystroglycan | |
| dcterms.subject | Neurosciences | |
| dcterms.subject | Ependymal Cell | |
| dcterms.subject | Developmental biology | |
| dcterms.subject | Laminin | |
| dcterms.subject | Neural Stem Cell | |
| dcterms.subject | Notch | |
| dcterms.subject | Subventricular Zone | |
| dcterms.title | Dystroglycan is a Novel and Context-Dependent Regulator of Notch in the Postnatal Subventricular Zone | |
| dcterms.type | Dissertation | |
