Graduation Year
2023
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Medical Sciences
Major Professor
Yao Yao, Ph.D.
Committee Member
Jerome Breslin, Ph.D.
Committee Member
Lianchun Wang, M.D.
Committee Member
Laura J. Blair, Ph.D.
Keywords
Blood-brain Barrier, Basement Membrane, Transcytosis, Myelination
Abstract
Oligodendrocyte lineage is a glial cell population in the central nervous system. The lineage starts with oligodendrocyte precursor cells, which differentiate and mature into mature oligodendrocytes. Myelination, the major function of mature oligodendrocytes, plays a significant role for normal function of the central nervous system, and its dysfunction leads to many demyelinating diseases, such as multiple sclerosis. During the lineage progression, an extracellular matrix protein, laminin, actively regulates the cells' biology, including cell proliferation, differentiation, and myelination. However, the cellular sources of the laminin that controls oligodendrocyte lineage cells remain largely unknown. Interestingly, previous studies have shown that oligodendrocyte lineage cells themselves make different laminin chains.
To investigate the functions of oligodendrocyte lineage-derived laminins, our laboratory has generated multiple conditional knockout mouse lines that target different chains of oligodendrocyte lineage-derived laminin (α5 and γ1 chains). Using the laminin γ1 knockout mouse line, we found that oligodendrocyte lineage-derived laminin γ1 is crucial for maintaining blood-brain barrier integrity through inhibiting transcytosis across endothelial cells. Furthermore, we found that oligodendrocyte lineage-derived laminin γ1 promotes proliferation, differentiation, and myelination of oligodendrocyte lineage cells. In sharp contrast, our study using the laminin α5 knockout mouse lines revealed that oligodendrocyte lineage-derived laminin α5 is dispensable for blood-brain barrier integrity maintenance and oligodendrocyte lineage biology under homeostatic and intracerebral stroke conditions.
Chapter 1 and Chapter 2 of this dissertation include a literature review of the roles of laminin in regulating oligodendrocyte biology and our experimental work that demonstrates the important functions of oligodendrocyte lineage-derived laminin γ1 for blood-brain barrier integrity maintenance and oligodendrocyte lineage biology. Chapter 3 and Chapter 4 include a literature review of oligodendrocyte biology under intracerebral hemorrhagic stroke conditions and our experimental work that shows the dispensable roles of oligodendrocyte lineage-derived laminin α5 under homeostatic and intracerebral hemorrhage conditions. Lastly Chapter 5 includes a literature review of how basement membrane components change in ischemic stroke, suggesting an area of future work for oligodendrocyte lineage-derived laminins. Together, this dissertation provides valuable insight to the fields of oligodendrocyte and laminin biology by unveiling the functions of oligodendrocyte lineage-derived laminins.
Scholar Commons Citation
Kang, Minkyung, "The Functions of Oligodendrocyte Lineage-derived Laminins under Homeostatic and Intracerebral Hemorrhagic Stroke Conditions" (2023). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/10814
