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Erk Signaling Dynamics and Their Role in Germ Layer Patterning.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Erk Signaling Dynamics and Their Role in Germ Layer Patterning./
Author:	McFann, Sarah E.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2022,
Description:	239 p.
Notes:	Source: Dissertations Abstracts International, Volume: 83-12, Section: B.
Contained By:	Dissertations Abstracts International83-12B.
Subject:	Developmental biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29066684
ISBN:	9798802750230

Erk Signaling Dynamics and Their Role in Germ Layer Patterning.
McFann, Sarah E.

Erk Signaling Dynamics and Their Role in Germ Layer Patterning. - Ann Arbor : ProQuest Dissertations & Theses, 2022 - 239 p.

Source: Dissertations Abstracts International, Volume: 83-12, Section: B.

Thesis (Ph.D.)--Princeton University, 2022.

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

While living creatures possess many different cell types, only a handful of core signaling pathways are required for developmental patterning, meaning that the effectors of these pathways are interpreted differently in different contexts. One way such differential interpretation can be achieved is through enhancer-level interpretation of signaling dynamics. In this work, we investigate the mechanisms used to generate and interpret phosphorylated Erk, a time-varying developmental signal, in the context of germ layer patterning, one of the first cell specification events to occur in development. First, we examine how mutations alter Erk signaling dynamics in vitro and find that mutations to Erk's activator, MEK, can overactivate the pathway through multiple means: by altering the way MEK interacts with Erk, and by altering the way MEK interacts with its own activator, Raf (Chapter 2). We then address the question of how Erk signaling dynamics are interpreted during germ layer specification-the choice to become either endoderm, mesoderm, or ectoderm (Chapter 3, Chapter 4). In Chapter 3, we optogenetically alter the duration of Erk signaling in Drosophila embryos and identify a critical time window during which cells decide whether to become endoderm or mesoderm. In Chapter 4, we examine how differences in enhancer sensitivity among genes are used to interpret Erk signaling level in the endoderm vs. ectoderm decision. Finally, in Chapter 5, we compare and contrast Erk signal interpretation in Drosophila and vertebrate mesodermal specification. We believe that this work, which pairs signal perturbation with transcriptional quantification, characterization of cellular behavior, and mechanistic modeling, brings us one step closer to a mechanistic understanding of how cells interpret time-varying signals in developmental contexts.

ISBN: 9798802750230Subjects--Topical Terms:

592588
Developmental biology.
Subjects--Index Terms:

Development

Erk Signaling Dynamics and Their Role in Germ Layer Patterning.
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100 1 $a McFann, Sarah E. $3 3689362
245 1 0 $a Erk Signaling Dynamics and Their Role in Germ Layer Patterning.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2022
300 $a 239 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-12, Section: B.
500 $a Includes supplementary digital materials.
500 $a Advisor: Toettcher, Jared E.;Shvartsman, Stanislav Y.
502 $a Thesis (Ph.D.)--Princeton University, 2022.
506 $a This item must not be sold to any third party vendors.
520 $a While living creatures possess many different cell types, only a handful of core signaling pathways are required for developmental patterning, meaning that the effectors of these pathways are interpreted differently in different contexts. One way such differential interpretation can be achieved is through enhancer-level interpretation of signaling dynamics. In this work, we investigate the mechanisms used to generate and interpret phosphorylated Erk, a time-varying developmental signal, in the context of germ layer patterning, one of the first cell specification events to occur in development. First, we examine how mutations alter Erk signaling dynamics in vitro and find that mutations to Erk's activator, MEK, can overactivate the pathway through multiple means: by altering the way MEK interacts with Erk, and by altering the way MEK interacts with its own activator, Raf (Chapter 2). We then address the question of how Erk signaling dynamics are interpreted during germ layer specification-the choice to become either endoderm, mesoderm, or ectoderm (Chapter 3, Chapter 4). In Chapter 3, we optogenetically alter the duration of Erk signaling in Drosophila embryos and identify a critical time window during which cells decide whether to become endoderm or mesoderm. In Chapter 4, we examine how differences in enhancer sensitivity among genes are used to interpret Erk signaling level in the endoderm vs. ectoderm decision. Finally, in Chapter 5, we compare and contrast Erk signal interpretation in Drosophila and vertebrate mesodermal specification. We believe that this work, which pairs signal perturbation with transcriptional quantification, characterization of cellular behavior, and mechanistic modeling, brings us one step closer to a mechanistic understanding of how cells interpret time-varying signals in developmental contexts.
590 $a School code: 0181.
650 4 $a Developmental biology. $3 592588
650 4 $a Bioengineering. $3 657580
650 4 $a Applied mathematics. $3 2122814
653 $a Development
653 $a Dynamics
653 $a MAPK
653 $a Modeling
653 $a Optogenetics
653 $a Signaling
690 $a 0758
690 $a 0202
690 $a 0364
710 2 $a Princeton University. $b Chemical and Biological Engineering. $3 2094012
773 0 $t Dissertations Abstracts International $g 83-12B.
790 $a 0181
791 $a Ph.D.
792 $a 2022
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29066684