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Study of the Role of EGL-38 PAX in the Developing Egg-Laying System and Germline Cell Survival in Caenorhabditis Elegans

Rajakumar, Vandana
http://rave.ohiolink.edu/etdc/view?acc_num=osu1166929817

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Molecular, Cellular, and Developmental Biology.
Understanding how genes coordinate the organization of cells into organs and how mutations in these genes upset this organization are fundamental questions in both cancer research and developmental biology. PAX factors play important roles to coordinate the development of mammalian organs like the kidney, eye and thyroid. The disruption of PAX activity leads to diseases like renal-coloboma syndrome and cancers in mammals. Dissecting the different functions for these factors has been difficult due to the complexity of organ development. To better understand these processes at a cellular level, I studied the role of a Pax2/5/8 transcription factor, EGL-38 in the developing egg-laying system and in the survival of germline cells of the nematode, Caenorhabditis elegans. egl-38(n578) mutant animals exhibit of high levels of Programmed Cell Death (PCD) in the germline and the soma. Wild-type EGL-38 can transcriptionally regulate the bcl-2 gene, ced-9 in C . elegans. In this dissertation, I performed mosaic analysis for EGL-38 and found that its activity is required in both the germline and soma to promote germline cell survival. EGL-38 is also involved in the development of the C . elegans egg-laying system. The egl-38(n578) mutants are egg-laying defective, so the eggs hatch within the hermaphrodite parent. The latter then bursts to release viable progeny. The C . elegans egg-laying system has two tissues, the somatic gonad and the vulva. The Pax2/5/8 transcription factor, EGL-38 is required for the normal development of the egg-laying system. Previously it was hypothesized to function in one tissue, the vulva to affect the development of both the vulval and somatic gonad tissues of the egg-laying system. While its mammalian counterpart, Pax 2 has independent functions in both the tissues of the metanephric kidney and thereby coordinates development between them. However, our studies involving various mutants and mosaic analysis demonstrate that egl-38 does have distinct functions in both the tissues of the egg-laying system of C . elegans. Furthermore, this influences both the autonomous and non-autonomous functions during the development of this system. Therefore, egl-38 behaves like the mammalian Pax2 by acting in the various tissues of an organ to promote its coordinated development. I also performed a genetic screen to isolate mutations in genes that suppress the egl-38(n578) egg-laying defect. Thereby I isolated four strong suppressor mutations. Two of these were mapped to separate locations on chromosome IV. Both these suppressor mutations suppress both the egg-laying defect and the elevated levels of cell death associated with the egl-38(n578) mutation. These studies have demonstrated that EGL-38 acts in multiple tissues to coordinate development like its mammalian counterpart Pax2 in the developing metanephric kidney. Thus there is conservation of the development logical by which PAX factors coordinate organogenesis. Finally, identifying the genes affected by the suppressor mutations could have implications in understanding development and survival of not only C . elegans but also of higher animals if these genes are evolutionarily conserved.
Helen Chamberlin (Advisor)
Biology, Genetics
organogenesis; PAX; EGL-38; suppressor

Recommended Citations

Citations

  • Rajakumar, V. (2007). Study of the Role of EGL-38 PAX in the Developing Egg-Laying System and Germline Cell Survival in Caenorhabditis Elegans [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1166929817

    APA Style (7th edition)

  • Rajakumar, Vandana. Study of the Role of EGL-38 PAX in the Developing Egg-Laying System and Germline Cell Survival in Caenorhabditis Elegans. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1166929817.

    MLA Style (8th edition)

  • Rajakumar, Vandana. "Study of the Role of EGL-38 PAX in the Developing Egg-Laying System and Germline Cell Survival in Caenorhabditis Elegans." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1166929817

    Chicago Manual of Style (17th edition)

osu1166929817
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This open access ETD is published by The Ohio State University and OhioLINK.