Type
Text
Type
Dissertation
Advisor
Mills, Alea A | Van Aelst, Linda , Tsirka, Styliani-Anna E | Dubnau, Joshua | Turner, Glenn.
Date
2012-08-01
Keywords
Neurosciences--Cellular biology--Molecular biology
Department
Department of Molecular and Cellular Biology
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/71466
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
The six-layered mammalian neocortex derives from a pseudostratified neuroepithelium by a series of cell divisions of neuronal progenitors, neuroepithelial and radial glial cells. Neurogenesis, a major event in the developing neocortex, relies on the ability of radial glial cells (RGCs) to switch from proliferative self-expanding to differentiative neurongenerating/progenitor self-renewing divisions. However, the molecular mechanisms that control this switch in a correct temporal manner are not well understood. In this thesis, I demonstrated that the DOCK180 family member DOCK7, an activator of Rac GTPases, plays an important role in the regulation of RGC proliferation versus differentiation. Silencing of DOCK7 in RGCs of developing mouse embryos hampers neuronal differentiation and maintains cells as cycling progenitors. Conversely, DOCK7 overexpression promotes RGC differentiation into basal progenitors and neurons. Using different approaches, including live-cell imaging experiments, I obtained evidence that DOCK7 influences RGC fate and neurogenesis by controlling the apically directed interkinetic nuclear migration (INM) process of RGCs. Importantly, DOCK7 exerts its effects on INM and neurogenesis independently of its GEF activity towards Rac, but instead does so by antagonizing the microtubule growth-promoting function of the centrosome-associated protein TACC3. Taken together, DOCK7 interacts with TACC3 to control INM, as such governing RGC fate and genesis of neurons during cortical development. | 116 pages
Recommended Citation
YANG, YUTING ROSA, "DOCK7 interacts with TACC3 to regulate interkinetic nuclear migration and genesis of neurons from cortical neuronal progenitors" (2012). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 672.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/672