東華大學圖書館 |

Function and Tissue Focus of daf-18/PTEN in Maintaining Blast Cell Multipotency and Quiescence in Caenorhabditis elegans Dauer Larvae.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Function and Tissue Focus of daf-18/PTEN in Maintaining Blast Cell Multipotency and Quiescence in Caenorhabditis elegans Dauer Larvae./
作者:	Tenen, Claudia.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	123 p.
附註:	Source: Dissertations Abstracts International, Volume: 80-10, Section: B.
Contained By:	Dissertations Abstracts International80-10B.
標題:	Physiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13856927
ISBN:	9781392056776

Function and Tissue Focus of daf-18/PTEN in Maintaining Blast Cell Multipotency and Quiescence in Caenorhabditis elegans Dauer Larvae.
Tenen, Claudia.

Function and Tissue Focus of daf-18/PTEN in Maintaining Blast Cell Multipotency and Quiescence in Caenorhabditis elegans Dauer Larvae. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 123 p.

Source: Dissertations Abstracts International, Volume: 80-10, Section: B.

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

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

Cellular quiescence, a reversible state of cell-cycle exit, and developmental potential, the ability to differentiate into appropriate cell types, are properties essential for normal development and stem cell function (reviewed in (Cheung and Rando, 2013; Fiore et al., 2018; Mihaylova et al., 2014). Understanding the mechanisms by which cells maintain quiescence has important implications for developmental biology, as this reversible state of cell-cycle exit is a key attribute of stem cells, as well as for cancer biology, as quiescence plays a key role in tumor dormancy and metastasis. Environmental conditions are key in regulating whether stem cells maintain quiescence or exit to resume divisions and developmentally progress. I aim to investigate how the properties of quiescence and developmental potential are retained over long periods of time and how they are appropriately regulated by external environmental inputs. The nematode Caenorhabditis elegans is an excellent model for investigating both of these questions because it is capable of entering and maintaining a developmentally arrested state for an unusually long time compared to the normal lifetime of the worm, and because the decision to enter this arrest is regulated entirely by external environmental inputs (Cassada and Russell, 1975). Upon encountering conditions unfavorable for growth, C. elegans enters an alternative, developmentally arrested state called dauer diapause in which precursor cells remain quiescent for months - a period many times the lifespan of a worm grown under favorable conditions (Cassada and Russell, 1975). Maintaining precursors in this arrested state is important in order for the worms to develop normally once conditions improve and requires components of the conserved Insulin/Insulin-like (IIS) signaling pathway (Karp and Greenwald 2013 and this work); of note, the IIS pathway also regulates mammalian quiescence (Eijkelenboom and Burgering, 2013). Canonical regulation of dauer diapause includes IIS, TGFs, and dafachronic acid (DA)/nuclear hormone receptor (NHR) signaling (reviewed in (Murphy and Hu, 2013a)). Here, I investigate how DAF-18, the sole C. elegans ortholog of the tumor suppressor PTEN (Phosphatase and tensin homolog) (Gil et al., 1999; Mihaylova et al., 1999; Ogg and Ruvkun, 1998; Rouault et al., 1999), maintains quiescence in dauer through regulation of these conserved signaling pathways using the C. elegans gonad as a model. The gonad is composed of somatic cells and the germline. Both the somatic gonad and germline develop post-embryonically from precursor cells present when dauer arrest occurs, and these precursor cells remain quiescent for the duration of dauer diapause (Cassada and Russell, 1975; Hong et al., 1998; Narbonne and Roy, 2006). After exit from dauer, division and differentiation resume. DAF-18/PTEN is required for germline quiescence during dauer diapause (Narbonne and Roy, 2006), and my results implicate DAF-18/PTEN in the control of quiescence of the somatic tissues as well, including the somatic gonad. In this role, DAF-18/PTEN activity in the somatic gonad non-autonomously coordinates both germline stem cell (GSC) and somatic gonad blast (SGB) quiescence. I have demonstrated this somatic gonad focus through mosaic analysis, tissue-specific rescue, and tissue-specific excision mosaics. We propose that DAF-18/PTEN mediates production of a signal promoting quiescence from the somatic gonad to the SGBs and GSCs and that this signal does not absolutely require or solely target the IIS, TGFβ, or DA/NHR signaling pathways normally implicated in regulation of dauer diapause.

ISBN: 9781392056776Subjects--Topical Terms:

518431
Physiology.
Subjects--Index Terms:

Developmental potential

Function and Tissue Focus of daf-18/PTEN in Maintaining Blast Cell Multipotency and Quiescence in Caenorhabditis elegans Dauer Larvae.
LDR:04901nmm a2200361 4500 001 2272455
005 20201105110058.5
008 220629s2019 ||||||||||||||||| ||eng d
020 $a 9781392056776
035 $a (MiAaPQ)AAI13856927
035 $a (MiAaPQ)columbia:15158
035 $a AAI13856927
040 $a MiAaPQ $c MiAaPQ
100 1 $a Tenen, Claudia. $3 3549894
245 1 0 $a Function and Tissue Focus of daf-18/PTEN in Maintaining Blast Cell Multipotency and Quiescence in Caenorhabditis elegans Dauer Larvae.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 123 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-10, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Greenwald, Iva.
502 $a Thesis (Ph.D.)--Columbia University, 2019.
506 $a This item must not be sold to any third party vendors.
520 $a Cellular quiescence, a reversible state of cell-cycle exit, and developmental potential, the ability to differentiate into appropriate cell types, are properties essential for normal development and stem cell function (reviewed in (Cheung and Rando, 2013; Fiore et al., 2018; Mihaylova et al., 2014). Understanding the mechanisms by which cells maintain quiescence has important implications for developmental biology, as this reversible state of cell-cycle exit is a key attribute of stem cells, as well as for cancer biology, as quiescence plays a key role in tumor dormancy and metastasis. Environmental conditions are key in regulating whether stem cells maintain quiescence or exit to resume divisions and developmentally progress. I aim to investigate how the properties of quiescence and developmental potential are retained over long periods of time and how they are appropriately regulated by external environmental inputs. The nematode Caenorhabditis elegans is an excellent model for investigating both of these questions because it is capable of entering and maintaining a developmentally arrested state for an unusually long time compared to the normal lifetime of the worm, and because the decision to enter this arrest is regulated entirely by external environmental inputs (Cassada and Russell, 1975). Upon encountering conditions unfavorable for growth, C. elegans enters an alternative, developmentally arrested state called dauer diapause in which precursor cells remain quiescent for months - a period many times the lifespan of a worm grown under favorable conditions (Cassada and Russell, 1975). Maintaining precursors in this arrested state is important in order for the worms to develop normally once conditions improve and requires components of the conserved Insulin/Insulin-like (IIS) signaling pathway (Karp and Greenwald 2013 and this work); of note, the IIS pathway also regulates mammalian quiescence (Eijkelenboom and Burgering, 2013). Canonical regulation of dauer diapause includes IIS, TGFs, and dafachronic acid (DA)/nuclear hormone receptor (NHR) signaling (reviewed in (Murphy and Hu, 2013a)). Here, I investigate how DAF-18, the sole C. elegans ortholog of the tumor suppressor PTEN (Phosphatase and tensin homolog) (Gil et al., 1999; Mihaylova et al., 1999; Ogg and Ruvkun, 1998; Rouault et al., 1999), maintains quiescence in dauer through regulation of these conserved signaling pathways using the C. elegans gonad as a model. The gonad is composed of somatic cells and the germline. Both the somatic gonad and germline develop post-embryonically from precursor cells present when dauer arrest occurs, and these precursor cells remain quiescent for the duration of dauer diapause (Cassada and Russell, 1975; Hong et al., 1998; Narbonne and Roy, 2006). After exit from dauer, division and differentiation resume. DAF-18/PTEN is required for germline quiescence during dauer diapause (Narbonne and Roy, 2006), and my results implicate DAF-18/PTEN in the control of quiescence of the somatic tissues as well, including the somatic gonad. In this role, DAF-18/PTEN activity in the somatic gonad non-autonomously coordinates both germline stem cell (GSC) and somatic gonad blast (SGB) quiescence. I have demonstrated this somatic gonad focus through mosaic analysis, tissue-specific rescue, and tissue-specific excision mosaics. We propose that DAF-18/PTEN mediates production of a signal promoting quiescence from the somatic gonad to the SGBs and GSCs and that this signal does not absolutely require or solely target the IIS, TGFβ, or DA/NHR signaling pathways normally implicated in regulation of dauer diapause.
590 $a School code: 0054.
650 4 $a Physiology. $3 518431
650 4 $a Developmental biology. $3 592588
653 $a Developmental potential
653 $a External environmental inputs
653 $a Somatic gonad
690 $a 0719
690 $a 0758
710 2 $a Columbia University. $b Cellular, Molecular and Biomedical Studies. $3 2099963
773 0 $t Dissertations Abstracts International $g 80-10B.
790 $a 0054
791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13856927