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Regional Contributions to Neuronal Diversity in the Developing Mouse Telencephalon

Qin, Shenyue
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505125562574288

Abstract Details

2017, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
The telencephalon located in the anterior portion of the central nervous system represents an essential developing structure that gives rise to a large variety of neurons and glia in the cortex and subcortical areas, which are vital for higher cognitive function, locomotion and emotion. While the dorsal telencephalon (i.e. pallium) produces projection neurons in the cortex, the ventral telencephalon (i.e. subpallium) generates large numbers of other neurons that populate both cortical and subcortical areas. The ventral telencephalon consists of multiple progenitor domains, including the lateral ganglionic eminence (LGE), the medial GE (MGE) and the septum, each of which produces highly diverse neuronal subtypes. Each progenitor domain in the ventral telencephalon is programmed differently and can be recognized by unique gene expression. The homeobox gene Gsx2 is widely expressed by subpallial progenitor cells located in the ventricular zone (VZ) and plays important roles in regulating normal subpallial development, including facilitating the establishment of dorsal-ventral (DV) boundary and controlling neurogenesis/gliogenesis in the LGE. Despite the important functions of Gsx2, little is known regarding how Gsx2 expression is controlled in the telencephalon. A transgenic mouse line expressing Cre and EGFP under the regulation of two putative cis-regulatory elements of Gsx2 was generated and partially recapitulated Gsx2 expression pattern, suggesting potentially important molecular control of Gsx2 in the telencephalon. In addition, the transgenic line drives robust recombination in the VZ of the LGE and the dorsal half of the MGE but not in the septum, providing a new genetic tool for gene manipulation in LGE progenitor cells. Olfactory bulb (OB) interneurons representing a neuronal type of great diversity are widely distributed in the OB, and are crucial for normal olfaction. Although it has been demonstrated that both LGE and septum give rise to OB interneurons, their contributions to OB interneuron diversity are still controversial. Using two novel genetic fate-mapping tools, the origin of OB interneuron diversity from LGE and septum at embryonic and neonatal time points was examined. Furthermore, a conditional knockout approach was taken to reveal that besides playing a crucial role in OB interneuron genesis from the LGE, Gsx2 was also found to be important for the normal generation of septum-derived OB interneurons. Finally, a Gsx2 missense mutation was recently identified in two patients with a mild mental retardation phenotype. A mouse line mimicking this mutation was created by CRIPSR technology and preliminary analysis suggests that nuclear localization of the mutant Gsx2 protein is intact. The novel missense mutation and the newly generated mouse line provide insight and a new tool for the molecular characterization of Gsx2.
Kenneth Campbell, Ph.D. (Committee Chair)
Brian Gebelein, Ph.D. (Committee Member)
A John MacLennan, Ph.D. (Committee Member)
Masato Nakafuku, M.D. Ph.D. (Committee Member)
Steven Potter, Ph.D. (Committee Member)
Ronald Waclaw, Ph.D. (Committee Member)
191 p.
Developmental Biology
Gsx2; cis-regulation; ventral telencephalon; basal ganglia; olfactory bulb; neurogenesis

Recommended Citations

Citations

  • Qin, S. (2017). Regional Contributions to Neuronal Diversity in the Developing Mouse Telencephalon [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505125562574288

    APA Style (7th edition)

  • Qin, Shenyue. Regional Contributions to Neuronal Diversity in the Developing Mouse Telencephalon. 2017. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505125562574288.

    MLA Style (8th edition)

  • Qin, Shenyue. "Regional Contributions to Neuronal Diversity in the Developing Mouse Telencephalon." Doctoral dissertation, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505125562574288

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Cincinnati and OhioLINK.