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Transcription Factor Regulation of Olfactory Bulb Interneuron Heterogeneity

Allen, Zegary J.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1273166739

Abstract Details

2010, PhD, University of Cincinnati, Medicine : Molecular and Developmental Biology.
Most regions of the brain lose the ability to generate new neurons shortly after birth. One exception to this rule is the interneurons of the olfactory bulb. In the mouse, these cells are generated beginning around embryonic day 13.5 and continue to be produced throughout adulthood. The ability to generate new neurons in the adult that can incorporate into existing networks makes this population a very attractive source of stem cells for neuronal replacement therapy. The studies of this thesis are aimed at determining how these cells are normally generated. Olfactory bulb interneurons are a very diverse population of cells that can be divided into three main types, a calretinin(CR) calbindin (CB) and tyrosine hydroxylase (TH) expressing population. Each population may have a unique set of transcription factors that are required for their proper generation. In order to aid in the elucidation of what transcription factors may be controlling subtype specification, a transcriptional code has been developed to identify the unique profiles of olfactory bulb interneurons. Characterization of the transcription factor Sp8 shows that it is expressed in progenitor regions known to give rise to olfactory bulb interneurons and its expression is maintained into mature interneurons. Interestingly, Sp8 is expressed in only a subset of cells in the olfactory bulb and virtually all CR positive interneurons. Conditional deletion of Sp8 reveals that it is also required for the normal generation of this population, while leaving other types mostly uneffected. Characterization of the winged-helix/forkhead transcription factor Foxp2 shows that it is also expressed in embryonic and postnatal regions known to give rise to olfactory bulb interneurons and is expressed in the CB positive interneurons. Using two models of Foxp2 loss of function reveals a novel role for Foxp2 in the production of CB positive cells. Finally, the homeobox transcription factor Pax6 has previously been shown to be required for the TH positive population of cells, which are Sp8 and Foxp2 negative. Conditional deletion of Pax6 confirms previous findings and reveals a novel role for Pax6 parallel to that of Foxp2 in generating CB positive cells. These results provide a framework to understanding the regulation of olfactory bulb interneuron generation.
Kenneth Campbell, PhD (Committee Chair)
Tiffany Cook, PhD (Committee Member)
Masato Nakafuku, MD, PhD (Committee Member)
Joseph Clark, PhD (Committee Member)
Nadean Brown, PhD (Committee Member)
195 p.
Molecular Biology
Olfactory bulb; interneurons; brain; development; mouse; transcription factor

Recommended Citations

Citations

  • Allen, Z. J. (2010). Transcription Factor Regulation of Olfactory Bulb Interneuron Heterogeneity [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1273166739

    APA Style (7th edition)

  • Allen, Zegary. Transcription Factor Regulation of Olfactory Bulb Interneuron Heterogeneity. 2010. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1273166739.

    MLA Style (8th edition)

  • Allen, Zegary. "Transcription Factor Regulation of Olfactory Bulb Interneuron Heterogeneity." Doctoral dissertation, University of Cincinnati, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1273166739

    Chicago Manual of Style (17th edition)

ucin1273166739
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This open access ETD is published by University of Cincinnati and OhioLINK.