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A Journey Through the Developing Kidney: Analysis of normal and Hoxa9,10,11-/-Hoxd9,10,11-/- Mouse Models

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2018, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
The kidney is a complex organ that is made of many different cell types. In an effort to better understand the cell diversity within the developing kidney we have performed single cell RNA-seq on embryonic day 14.5 mouse kidneys using Drop-seq, Chromium 10X Genomics, and Fluidigm C1 platforms. AltAnalyze was used to identify sixteen cell clusters; medullary collecting duct, cortical collecting duct, ureteric bud tip, loop of Henle, distal comma shaped body, podocyte, mid S-shaped body, early proximal tubule, pre-tubular aggregate, three cap mesenchyme groups, endothelium, nephrogenic zone stroma, cortical stroma, and medullary stroma. In addition to the known identifier genes, novel specific gene associations were also discovered during analysis. One such example is the discovery of Gdnf expression from within the stromal population, which was previously thought of as being exclusively expressed from the cap mesenchyme. The wild type single cell RNA-seq data set was also used to identify Hox gene expression within the developing kidney. Interestingly there is an apparent lack of a Hox code within the developing kidney, with thirty-six of the thirty-nine Hox genes being ubiquitously expressed throughout the kidney. Previous studies have determined that Hox 10 and 11 paralogous groups have functional redundancies within kidney development. Based on the expression data it is feasible that flanking genes are also functionally redundant within kidney development. These redundancies can mask the specific functions of individual Hox genes. For this reason Hoxa9,10,11; Hoxd9,10,11 mutants were used to further elucidate the role of Hox genes during kidney development. Morphological analysis of the Hox mutants shows alterations in mature nephron segment identity, medullary zone specification, and the lack of a pelvic opening. Obtaining a comprehensive single cell RNA-seq data set allows for the visualization of the expression profile of many genes within the wild type developing kidney. These data can then be used as an atlas for comparing mutant data sets. By combining the Hox mutant morphological phenotypes with the single cell expression profiles we can better understand the molecular regulation of kidney development.
Steven Potter, Ph.D. (Committee Chair)
Sudhansu Dey, Ph.D. (Committee Member)
Brian Gebelein, Ph.D. (Committee Member)
Ashish Kumar, M.D. Ph.D. (Committee Member)
Joo-Seop Park, Ph.D. (Committee Member)
93 p.

Recommended Citations

Citations

  • Magella, B. (2018). A Journey Through the Developing Kidney: Analysis of normal and Hoxa9,10,11-/-Hoxd9,10,11-/- Mouse Models [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1523629396626027

    APA Style (7th edition)

  • Magella, Bliss. A Journey Through the Developing Kidney: Analysis of normal and Hoxa9,10,11-/-Hoxd9,10,11-/- Mouse Models. 2018. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1523629396626027.

    MLA Style (8th edition)

  • Magella, Bliss. "A Journey Through the Developing Kidney: Analysis of normal and Hoxa9,10,11-/-Hoxd9,10,11-/- Mouse Models." Doctoral dissertation, University of Cincinnati, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1523629396626027

    Chicago Manual of Style (17th edition)