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Molecular mechanisms of olfactory neuron diversification in C. elegans

Alqadah, Amel

Abstract Details

2016, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
Cellular diversity within the nervous system is fundamental for our capability to perform intricate functions, experience various emotions, formulate complex thoughts, and sense and respond to our environment. The immense complexity of the nervous system has rendered research into the molecular mechanisms underlying neuronal diversity especially challenging, and much remains to be understood on how different neuronal subtypes are specified. Work in this thesis presents two different modes of neuronal diversification: a left-right asymmetry genetic pathway to distinguish between neuronal subtypes, and use of a common terminal selector to specify two different lineally unrelated sensory neurons using C. elegans as a model organism. I show that voltage and calcium activated potassium channels SLO-1 and SLO-2 act redundantly in a left-right asymmetry genetic pathway to distinguish between the AWCON; and AWCOFF neuronal subtypes. The potassium channels serve as a molecular link between gap junctions and calcium signaling to promote a terminal neuronal identity. In addition, I identify a function of an importin protein in transporting a homeodomain transcription factor into the nucleus of AWC for promoting left-right asymmetry. Next, I show that the well-known and conserved stem cell factor SOX-2 functions as a terminal selector for two distinct olfactory neuron types AWB and AWC, and interacts with two different transcription factors in a cell context-dependent manner to distinguish between their terminal identities. Finally, I describe results of forward genetic screens used to identify novel players in the left-right asymmetry and the AWB-AWC neuronal diversification pathway. Mechanisms described in this thesis may be conserved in vertebrates and may further our understanding of how neuronal subtypes are diversified.
Chiou-fen Chuang, Ph.D. (Committee Chair)
Jun Ma, Ph.D. (Committee Member)
Iain Cartwright, Ph.D. (Committee Member)
Chieh Chang, Ph.D. (Committee Member)
James Wells, Ph.D. (Committee Member)
275 p.

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Citations

  • Alqadah, A. (2016). Molecular mechanisms of olfactory neuron diversification in C. elegans [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1455208834

    APA Style (7th edition)

  • Alqadah, Amel. Molecular mechanisms of olfactory neuron diversification in C. elegans. 2016. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1455208834.

    MLA Style (8th edition)

  • Alqadah, Amel. "Molecular mechanisms of olfactory neuron diversification in C. elegans." Doctoral dissertation, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1455208834

    Chicago Manual of Style (17th edition)