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Investigating the Role of the Oocyte...

Hubbard, Nisan M.

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Investigating the Role of the Oocyte and Jag1 in Notch Activation in the Mammalian Ovary.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Investigating the Role of the Oocyte and Jag1 in Notch Activation in the Mammalian Ovary./
作者:	Hubbard, Nisan M.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	270 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-08, Section: B.
Contained By:	Dissertations Abstracts International81-08B.
標題:	Biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27662762
ISBN:	9781392627037

Investigating the Role of the Oocyte and Jag1 in Notch Activation in the Mammalian Ovary.
Hubbard, Nisan M.

Investigating the Role of the Oocyte and Jag1 in Notch Activation in the Mammalian Ovary. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 270 p.

Source: Dissertations Abstracts International, Volume: 81-08, Section: B.

Thesis (Ph.D.)--Northwestern University, 2019.

This item must not be sold to any third party vendors.

The ovarian follicle serves a functional niche for oocyte development through bidirectional communication that occurs between the somatic and germ cells. The follicle progresses through its formation and growth via coordination between somatic pre-granulosa cells and oocytes. These cells together form the initial primordial follicles, which establish the reproductive lifespan of the organism. Successful follicle establishment requires proper signaling, including mechanisms involving direct contact between the granulosa cells and oocytes. This thesis explores these mechanisms of contact-dependent signaling by investigating the initial activation of the Notch juxtacrine signaling pathway in the ovary during follicle development.The Notch pathway plays diverse and complex roles in cell signaling during development. In the mammalian ovary, Notch is important for the initial formation and growth of follicles, and for regulating the proliferation and differentiation of follicular granulosa cells in preovulatory follicles. This study seeks to determine the contribution of female germ cells toward the initial activation and subsequent maintenance of Notch signaling within somatic granulosa cells of the ovary. Transgenic Notch Reporter (TNR) mice were crossed with Sohlh1-mCherry (S1CF) transgenic mice to visualize Notch active cells (EGFP) and germ cells (mCherry) simultaneously in the neonatal ovary. To test the involvement of oocytes in the activation of Notch signaling in ovarian somatic cells, I reduced germ cell numbers using Busulfan, a chemotherapeutic alkylating agent, or I investigated KitWv/Wv (viable dominant white-spotting) mice that lack most germ cells.The data reveal that Notch pathway activation in granulosa cells, measured with the EGFP reporter, is significantly suppressed when germ cells are reduced in TNR/S1CF mice during late embryogenesis or in the TNR/KitWv/Wv mice during early postnatal development. Oocyte depletion, measured by Vasa or Jag1 gene expression, was associated with significant suppression of multiple Notch target genes as well as the Egfp Notch reporter. Imaging studies revealed that EGFP expression is more intense in those somatic cells in proximity to germ cells, although there is residual EGFP activity in the ovary that appears to be independent of associated germ cells. Disruption of the gene for the Notch ligand Jag1 in oocytes similarly impacts Notch activation in the ovary, as assessed with the TNR Notch reporter, consistent with the hypothesis that germ cells provide a ligand, such as Jag1, that is necessary for the activation of Notch signaling in the developing ovary. Overall, these experiments provide new insights into the interactions between germ cells and somatic cells that lead to activation of Notch signaling, a pathway known to be important in the formation and subsequent maturation of ovarian follicles. Such knowledge of fundamental signaling processes in the mouse ovary may be relevant to better understanding female disorders impacting fertility and their treatment.

ISBN: 9781392627037Subjects--Topical Terms:

522710
Biology.
Subjects--Index Terms:

Jag1

Investigating the Role of the Oocyte and Jag1 in Notch Activation in the Mammalian Ovary.
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300 $a 270 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-08, Section: B.
500 $a Advisor: Mayo, Kelly E.;LaBonne, Carole.
502 $a Thesis (Ph.D.)--Northwestern University, 2019.
506 $a This item must not be sold to any third party vendors.
520 $a The ovarian follicle serves a functional niche for oocyte development through bidirectional communication that occurs between the somatic and germ cells. The follicle progresses through its formation and growth via coordination between somatic pre-granulosa cells and oocytes. These cells together form the initial primordial follicles, which establish the reproductive lifespan of the organism. Successful follicle establishment requires proper signaling, including mechanisms involving direct contact between the granulosa cells and oocytes. This thesis explores these mechanisms of contact-dependent signaling by investigating the initial activation of the Notch juxtacrine signaling pathway in the ovary during follicle development.The Notch pathway plays diverse and complex roles in cell signaling during development. In the mammalian ovary, Notch is important for the initial formation and growth of follicles, and for regulating the proliferation and differentiation of follicular granulosa cells in preovulatory follicles. This study seeks to determine the contribution of female germ cells toward the initial activation and subsequent maintenance of Notch signaling within somatic granulosa cells of the ovary. Transgenic Notch Reporter (TNR) mice were crossed with Sohlh1-mCherry (S1CF) transgenic mice to visualize Notch active cells (EGFP) and germ cells (mCherry) simultaneously in the neonatal ovary. To test the involvement of oocytes in the activation of Notch signaling in ovarian somatic cells, I reduced germ cell numbers using Busulfan, a chemotherapeutic alkylating agent, or I investigated KitWv/Wv (viable dominant white-spotting) mice that lack most germ cells.The data reveal that Notch pathway activation in granulosa cells, measured with the EGFP reporter, is significantly suppressed when germ cells are reduced in TNR/S1CF mice during late embryogenesis or in the TNR/KitWv/Wv mice during early postnatal development. Oocyte depletion, measured by Vasa or Jag1 gene expression, was associated with significant suppression of multiple Notch target genes as well as the Egfp Notch reporter. Imaging studies revealed that EGFP expression is more intense in those somatic cells in proximity to germ cells, although there is residual EGFP activity in the ovary that appears to be independent of associated germ cells. Disruption of the gene for the Notch ligand Jag1 in oocytes similarly impacts Notch activation in the ovary, as assessed with the TNR Notch reporter, consistent with the hypothesis that germ cells provide a ligand, such as Jag1, that is necessary for the activation of Notch signaling in the developing ovary. Overall, these experiments provide new insights into the interactions between germ cells and somatic cells that lead to activation of Notch signaling, a pathway known to be important in the formation and subsequent maturation of ovarian follicles. Such knowledge of fundamental signaling processes in the mouse ovary may be relevant to better understanding female disorders impacting fertility and their treatment.
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650 4 $a Cellular biology. $3 3172791
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653 $a Oocytes
653 $a Ovaries
653 $a Reproductive biology
690 $a 0306
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710 2 $a Northwestern University. $b Interdepartmental Biological Sciences (IBiS) Graduate Program. $3 3288393
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