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Development of cloacal organs in mouse and human

Method, Anna M
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1384425968

Abstract Details

2013, MS, University of Cincinnati, Medicine: Molecular and Developmental Biology.
The cloaca is a transient embryonic structure that develops from the posterior hindgut that gives rise to the endodermal lining of the rectum, anus, and the urogenital system, including the bladder and urethra through a process known as septation. When this does not occur properly it can lead to anorectal and urogenital malformations, varying in severity from a simple fistula to complex anomalies like cloaca malformation. The developmental process of septation is poorly understood and the complex nature of these defects leaves much room for therapeutic treatment improvement. An overall lack of early cloacal markers makes identifying progenitor cells as well as following the identity of regions of the cloaca during development difficult. After identifying useful cloacal markers, K8 and Sox2, looking at the expression pattern during early development in mouse from e8.5 to e15.5, we mapped early cloacal domains that give rise to bladder, urethra, and parts of the anorectal system. We used these newly defined markers to establish a model of human cloaca development using a recently published method to derive gut tube structures (spheroids) from human embryonic stem cells. Given that the cloaca develops from the posterior hindgut, we hypothesized that posteriorizing factors could direct three dimensional spheroids into organoids containing cloacal progenitors that would form differentiated cells of the urogenital and anorectal tracts. Our data suggests that timing and dose of Wnt and BMP signaling posteriorized gut tube spheroids and that this promoted the subsequent formation of urothelial lineages. The ability to generate cloacal progenitors and its derivates will allow study of anorectal and urogenital malformations in a human in vitro system, which could lead to new therapeutic treatments.
James Wells, Ph.D. (Committee Chair)
Geraldine Guasch, Ph.D. (Committee Member)
Aaron Zorn, Ph.D. (Committee Member)
76 p.
Developmental Biology
cloaca; urogenital; hindgut; BMP; human embryonic stem cells; anorectal malformation

Recommended Citations

Citations

  • Method, A. M. (2013). Development of cloacal organs in mouse and human [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1384425968

    APA Style (7th edition)

  • Method, Anna. Development of cloacal organs in mouse and human. 2013. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1384425968.

    MLA Style (8th edition)

  • Method, Anna. "Development of cloacal organs in mouse and human." Master's thesis, University of Cincinnati, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1384425968

    Chicago Manual of Style (17th edition)

ucin1384425968
363
© 2013, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.