Date of Completion

Spring 5-1-2024

Thesis Advisor(s)

Joanne Conover

Honors Major

Physiology and Neurobiology

Disciplines

Cellular and Molecular Physiology | Developmental Neuroscience

Abstract

Stem cells in the lateral ventricles of the brain undergo a process of development within the ventricular-subventricular zone. In early development neuroepithelial cells divide to form more neuroepithelial cells or convert to radial glial cells (RGCs). These RGCs, or stem cells, then divide to form neurons or other glial cells such as ependymal cells, which form a single-layered ependyma along the ventricular wall. These stem cells divide in two ways: symmetrically, producing two ependymal cells or asymmetrically, yielding one neural stem cell and ependymal cell. To further study this process the Cre-lox system in mice will be used. By breeding homozygous Cre-Lox and Lox-P mice a transgenic mouse line will be developed to express the Cre recombinase enzyme. This enzyme modifies genes positioned between two LoxP sites. It will be placed downstream from a Nestin promoter, as Nestin is only expressed in stem cells. This ensures that all cells that contain the Cre enzyme will be Nestin+, and therefore cells of interest. Tamoxifen will be used to trigger the Cre-Lox system and label Nestin+ neural stem cells (NSCs), followed by tissue harvesting 24 hours later. The Nestin Cre-lox system allows us to quantify the cell division patterns that lead to the formation of the ependymal lining. This research seeks to deepen understanding of ependymogenesis and neurogenesis during brain development and into adulthood. Insights gained could have implications for understanding diseases that affect the brain's ventricular system, as stem cells play a critical role through their involvement in generating new neurons.

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