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A Novel Role for Endothelial Rbpj in Postnatal Cerebellum Morphogenesis

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2018, Bachelor of Science (BS), Ohio University, Biological Sciences.
Brain Arteriovenous Malformation (AVM) is a human disease with clinically defined vascular abnormalities, such as arteriovenous shunting. This shunting allows arterial blood to flow directly to a vein; bypassing capillaries and affecting gas exchange in the affected tissue. We use a genetic mouse model of brain AVM to study the disease pathogenesis, which proceeds during the early postnatal period, just after birth. This time window coincides with postnatal cerebellum development and includes events such as cerebellar lobulation, lamination, and circuitry formation. Interestingly, 100% of our brain AVM mice have similar cerebellar abnormalities. While the cerebellar defects may be a secondary consequence of the vascular abnormalities (e.g. impaired oxygen delivery to brain tissue), they may also be a primary consequence of impaired Notch/Rbpj signaling between endothelial cells (ECs) and other cell types in the brain. We hypothesize that endothelial Rbpj is required for postnatal cerebellar morphogenesis and laminar organization. To study this, we deleted Rbpj selectively in ECs and examined cerebellar defects. We found significantly decreased cerebellar area, decreased molecular layer thickness, along the sides and tips of select cerebellar lobules, as well as decreased fissure length between lobules, suggesting impaired outward growth of postnatal cerebellum. We also found reduced number of Purkinje neurons in the Purkinje cell layer of the cerebellum, suggesting that abnormal cerebellar lamination. Our data suggest that Rbpj is required regionally in postnatal ECs for proper cerebellar morphogenesis and laminar organization.
Corinne Nielsen, Ph.D. (Advisor)
73 p.

Recommended Citations

Citations

  • Chapman, A. D. (2018). A Novel Role for Endothelial Rbpj in Postnatal Cerebellum Morphogenesis [Undergraduate thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1524778255730872

    APA Style (7th edition)

  • Chapman, Amelia. A Novel Role for Endothelial Rbpj in Postnatal Cerebellum Morphogenesis. 2018. Ohio University, Undergraduate thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1524778255730872.

    MLA Style (8th edition)

  • Chapman, Amelia. "A Novel Role for Endothelial Rbpj in Postnatal Cerebellum Morphogenesis." Undergraduate thesis, Ohio University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1524778255730872

    Chicago Manual of Style (17th edition)