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Lymphangiogenesis in the Developing Zebrafish

Coffindaffer-Wilson, Mikah
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1318861912

Abstract Details

2011, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
The lymphatic vascular system is critical for several key physiological functions including maintenance of fluid homeostasis by absorbing water and macromolecules from the interstitium, uptake of dietary lipids and fat soluble vitamins, and trafficking of immune cells. There are several diseases in which the lymphatic system is involved. Malformation or lack of lymphatic vasculature causes lymphedema, a debilitating and disfiguring disease that dramatically decreases quality of life. Overproduction of lymphatic vessels can lead to formation of lymphatic malformations. Other diseases associated with the lymphatic system include trafficking and migration of cancer cells and also its role in altered lipid transport, which is associated with obesity and aggravation of inflammatory bowel disorders such as Crohn’s Disease. Although there are many diseases associated with the lymphatic system, with results ranging from severely diminishing quality of life to death, comprehensive understanding of these diseases and cures for them remains elusive. Development of curative treatments for these diseases will first require a better scientific understanding of the patterns and processes of lymphatic development. The goal of this work is to further the field of developmental lymphangiogenesis by first describing the spatial and temporal emergence of developing lymphatic vessels in the zebrafish model organism. Zebrafish are particularly amendable to studies of developmental lymphangiogenesis due to their ex utero development, allowing direct optical access to nascent lymphatic vessels as they form within the living embryo. The anatomical mapping of zebrafish lymphatics will facilitate its use by researchers as we iv continue to make strides in this poorly understood area of vascular research. The anatomical mapping also led to the discovery of the supra-intestinal lymphatic vessel (SIL), which has the potential to open new avenues for understanding how dietary lipids are absorbed and may have implications that the zebrafish could be utilized to study the connection of the lymphatic system in lipid uptake and obesity. Once the spatiotemporal anatomy of the zebrafish was mapped, we began to explore the role of extracellular fluid on the emergence and development of this vascular network. We discovered normal interstitial flow patterns are critical for proper lymphatic vascular development. Experimentally increasing or decreasing the velocity of interstitial flow, via alterations in blood pressure, ablates the normal formation of the thoracic duct (the primary lymphatic vessel in the zebrafish). The loss of lymphatic vessel development under conditions of both increased and decreased hydrodynamic forces suggest that fluid flow may be helping to establish and maintain an appropriate biomorphological gradient which serves as a migratory cue for the LEC translocation from the parachordal vessel to the site of eventual coalescence and vessel assembly. While our collective understanding of lymphatic development is far from comprehensive, it is our hope that this work will aid in furthering the field to ultimately find cures for those that suffer from lymphatic system disease.
Jay Hove, PhD (Committee Chair)
Denise Adams, MD (Committee Member)
Ann Akeson, PhD (Committee Member)
Saulius Sumanas, PhD (Committee Member)
Patrick P.W. Tso, PhD (Committee Member)
Katherine Yutzey, PhD (Committee Member)
144 p.
Molecular Biology
Lymphangiogenesis; Zebrafish; Interstitial Flow; Lymphatic

Recommended Citations

Citations

  • Coffindaffer-Wilson, M. (2011). Lymphangiogenesis in the Developing Zebrafish [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1318861912

    APA Style (7th edition)

  • Coffindaffer-Wilson, Mikah. Lymphangiogenesis in the Developing Zebrafish. 2011. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1318861912.

    MLA Style (8th edition)

  • Coffindaffer-Wilson, Mikah. "Lymphangiogenesis in the Developing Zebrafish." Doctoral dissertation, University of Cincinnati, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1318861912

    Chicago Manual of Style (17th edition)

ucin1318861912
701
© 2011, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.