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Role of Proto-oncogenes, Pi3K, Her2,...

Erler, Piril.

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Role of Proto-oncogenes, Pi3K, Her2, Braf and Yap1 and Adult Stem Cells in Regeneration.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Role of Proto-oncogenes, Pi3K, Her2, Braf and Yap1 and Adult Stem Cells in Regeneration./
Author:	Erler, Piril.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
Description:	118 p.
Notes:	Source: Dissertation Abstracts International, Volume: 78-09(E), Section: B.
Contained By:	Dissertation Abstracts International78-09B(E).
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10272594
ISBN:	9781369760088

Role of Proto-oncogenes, Pi3K, Her2, Braf and Yap1 and Adult Stem Cells in Regeneration.
Erler, Piril.

Role of Proto-oncogenes, Pi3K, Her2, Braf and Yap1 and Adult Stem Cells in Regeneration. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 118 p.

Source: Dissertation Abstracts International, Volume: 78-09(E), Section: B.

Thesis (Ph.D.)--Northeastern University, 2017.

Neither the molecular mechanisms responsible for regeneration nor the capacity of plastic cells are fully elucidated in highly regenerative animals. These animals excel at tapping into developmental programs and utilize their plastic cell populations time after time. There is evidence that the axolotl can regenerate its limbs, tail, heart, brain, liver, spinal cord and skin, yet regenerative capacity and method of regeneration is unknown for other organs. Although axolotls can recurrently regenerate complex tissues, they are resistant to cancer. My dissertation work first describes the previous literature on mechanisms utilized in limb regeneration, both on a cellular and genetic context. This summarizes our knowledge regarding stress factors, miRNA function, epigenetic modifications and signaling transduction in response to the loss of the limb. Next, I focus on elucidating the role of signaling pathway molecules such as Kras, Braf, Her2, Pi3k and Yap that are upregulated during tumorigenesis but have not been described in axolotl organ, tail and limb regeneration. We show that during normal regeneration, these proto-oncogenes are elevated in basal keratinocytes, satellite stem cells, specialized muscle cells, mesenchymal and blastema cells. Furthermore, I provide evidence that each of these proto-oncogenes are indispensable for limb regeneration due to their role in regulating the blastema cells and the epidermal cap. Moreover, I show that transgenic models can be used to study the source of resistance to oncogenesis with constructs that integrate human oncogenes into the axolotl genome. In the final portion of my dissertation, I investigate adult stem cells during ovarian regeneration. I demonstrate genetic mechanisms responsible for ovarian regeneration and identify adult stem cells used in this process. Through this investigation, we reveal that adult ovarian tissue of the axolotl is comparable to mammalian ovaries in their expression of stem cell markers Sox2, Oct4, Nanog and germline markers Vasa, PiwiL1, PiwiL2, Lhx8, DazL, and Bmp15. Our evidence on activation of adult ovarian stem cells suggests that the axolotl may serve as an outstanding ovarian regeneration model for reproductive medicine. Moreover, we suggest that the axolotl can also become an important cancer resistance model to decipher how repeatedly generating tissues, using these oncogenic mechanisms, do not yield in a tumor prone environment and oncogenesis.

ISBN: 9781369760088Subjects--Topical Terms:

3172791
Cellular biology.

Role of Proto-oncogenes, Pi3K, Her2, Braf and Yap1 and Adult Stem Cells in Regeneration.
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