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Gene Regulatory Networks Controlling...

Clark, Natalie Minako.

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Gene Regulatory Networks Controlling Multicellular Development.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Gene Regulatory Networks Controlling Multicellular Development./
作者:	Clark, Natalie Minako.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:	341 p.
附註:	Source: Dissertation Abstracts International, Volume: 80-03(E), Section: B.
Contained By:	Dissertation Abstracts International80-03B(E).
標題:	Botany. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=11007075
ISBN:	9780438597693

Gene Regulatory Networks Controlling Multicellular Development.
Clark, Natalie Minako.

Gene Regulatory Networks Controlling Multicellular Development. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 341 p.

Source: Dissertation Abstracts International, Volume: 80-03(E), Section: B.

Thesis (Ph.D.)--North Carolina State University, 2018.

Development in multicellular organisms requires not only the production of specialized cell types but also mechanisms of coordination among them. Stem cells are ultimately the source of all cell types, and the balance between self-renewal and differentiation of their progeny regulates organ growth. Transcription factors and cell-to-cell signaling have a key role in coordinating these processes; however, how these transcriptional networks control multicellular development is not completely understood. Here, I investigate how we can use Gene Regulatory Network (GRN) inference to identify the genes, and the relationships among them, that are important for multicellular development.

ISBN: 9780438597693Subjects--Topical Terms:

516217
Botany.

Gene Regulatory Networks Controlling Multicellular Development.
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520 $a Development in multicellular organisms requires not only the production of specialized cell types but also mechanisms of coordination among them. Stem cells are ultimately the source of all cell types, and the balance between self-renewal and differentiation of their progeny regulates organ growth. Transcription factors and cell-to-cell signaling have a key role in coordinating these processes; however, how these transcriptional networks control multicellular development is not completely understood. Here, I investigate how we can use Gene Regulatory Network (GRN) inference to identify the genes, and the relationships among them, that are important for multicellular development.
520 $a First, I explore a GRN in the Arabidopsis root stem cells that involves the mobile transcription factor SHORTROOT (SHR) and its binding partner SCARECROW (SCR). I use scanning Fluorescence Correlation Spectroscopy (scanning FCS) techniques to quantify the movement of SHR protein from the vasculature, where it is transcribed, to the endodermis and Quiescent Center (QC), where it binds SCR. Using a combination of Raster Image Correlation Spectroscopy (RICS) and Pair Correlation Function (pCF) analysis, I show that the movement of SHR from the endodermis back to the vasculature is restricted by its binding to SCR. Additionally, using Number and Brightness (N&B), I observed that SHR and SCR form two different protein complex stoichiometries in the Cortex Endodermis Initials (CEI), but four different stoichiometries in the QC. To unravel how differences in SHR-SCR complex formation may affect its function in the CEI and QC, I build a mathematical model that predicts differences in SHR and SCR dynamics between the CEI and QC. Using the model prediction and a transcriptomic dataset of temporal gene expression in the root, I identify SEUSS (SEU) as a putative SHR activator and WUSCHEL RELATED HOMEOBOX 5 (WOX5) as a putative SHR repressor. My model, which incorporates this upstream SHR regulation, shows that high levels of the SHR-SCR complex trigger CEI division but repress QC division. This suggests new roles for SHR and SCR in controlling CEI and QC division.
520 $a Next, I show how scanning FCS techniques can be used to study development in another multicellular organism, namely Drosophila. In the Drosophila embryo, the transcription factor Dorsal (Dl) acts as a mobile signal to control embryo patterning and development along with its binding partner Cactus (Cact). Using RICS and pCF, I show that Dl movement is restricted on the ventral side of the embryo. We further show that this restriction of Dl movement is correlated with the proportion of Dl bound to DNA using cross-correlation RICS. Finally, using mathematical modeling, we show that the dorsal-ventral gradient of Dl movement depends on the proportion of Dl bound to DNA. Therefore, this combination of scanning FCS and mathematical modeling reveals how mobile signals control development in different multicellular organisms.
520 $a Finally, I show how computational methods can be used to predict GRNs from transcriptional data. I specifically focus on a regression tree analysis pipeline, named Regression Tree Pipeline for Spatial, Temporal, And Replicate Data (RTP-STAR), that can infer directed networks from steady state transcriptional data. I present how I used RTP-STAR to infer a GRN in Arabidopsis root hair cells. This inferred GRN led to a mathematical model which shows how a negative feedback loop between two key genes controls proper root hair growth. This pipeline has been incorporated into a graphical user interface named TuxNet that provides a simple methodology for biologists to infer GRNs from transcriptional data. Taken together, these studies that incorporate mathematical modeling, experimental data, and GRN inference have identified important genes and regulatory networks that control cell division and patterning in both Arabidopsis and Drosophila.
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