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Investigation of the Multiple Roles ...

Rabe, Brian A.

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Investigation of the Multiple Roles of Notch Signaling in Embryonic Retinal Development Using Novel High-Throughput Techniques.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Investigation of the Multiple Roles of Notch Signaling in Embryonic Retinal Development Using Novel High-Throughput Techniques./
Author:	Rabe, Brian A.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	235 p.
Notes:	Source: Dissertations Abstracts International, Volume: 82-09, Section: B.
Contained By:	Dissertations Abstracts International82-09B.
Subject:	Developmental biology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28315811
ISBN:	9798582571537

Investigation of the Multiple Roles of Notch Signaling in Embryonic Retinal Development Using Novel High-Throughput Techniques.
Rabe, Brian A.

Investigation of the Multiple Roles of Notch Signaling in Embryonic Retinal Development Using Novel High-Throughput Techniques. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 235 p.

Source: Dissertations Abstracts International, Volume: 82-09, Section: B.

Thesis (Ph.D.)--Harvard University, 2021.

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

The process by which cell diversity is created during development is a central question in developmental biology. One of the most diverse groups of cells, the cells of the nervous system, exemplify this diversification with a dizzying array of cell types that are still being identified. The retina, a part of the central nervous system, has served as a powerful model with which to study the process of cell type diversity generation in the nervous system. During development of the embryonic mouse retina, retinal progenitors can be broadly classified into three large classes, each fated to produce different cell types. The Notch signaling pathway, a pathway used throughout development, is known to regulate these fate decisions. However, the mechanism by which this pathway, often thought to be one of binary fate decisions, can regulate three different fates is unknown.In order to investigate this process, we used single-cell RNA sequencing to profile progenitors in the embryonic retinas. Using known markers for two of these progenitor classes, we identified all three. This analysis revealed a potential three-tiered model of Notch signaling, with each tier specifying one progenitor class through the regulation of two sequential fate decision points. We provide further evidence for this model using experimental simulation of a middle-level Notch signaling state, and add to our model mechanisms for how this middle state is achieved. This model is further supported with data collected using high-throughput enhancer discovery and analysis techniques that we developed, which also allow for the investigation of upstream transcriptional regulation in other systems.

ISBN: 9798582571537Subjects--Topical Terms:

592588
Developmental biology.
Subjects--Index Terms:

Development

Investigation of the Multiple Roles of Notch Signaling in Embryonic Retinal Development Using Novel High-Throughput Techniques.
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100 1 $a Rabe, Brian A. $0 (orcid)0000-0002-2058-1047 $3 3561761
245 1 0 $a Investigation of the Multiple Roles of Notch Signaling in Embryonic Retinal Development Using Novel High-Throughput Techniques.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2021
300 $a 235 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-09, Section: B.
500 $a Advisor: Cepko, Constance.
502 $a Thesis (Ph.D.)--Harvard University, 2021.
506 $a This item must not be sold to any third party vendors.
520 $a The process by which cell diversity is created during development is a central question in developmental biology. One of the most diverse groups of cells, the cells of the nervous system, exemplify this diversification with a dizzying array of cell types that are still being identified. The retina, a part of the central nervous system, has served as a powerful model with which to study the process of cell type diversity generation in the nervous system. During development of the embryonic mouse retina, retinal progenitors can be broadly classified into three large classes, each fated to produce different cell types. The Notch signaling pathway, a pathway used throughout development, is known to regulate these fate decisions. However, the mechanism by which this pathway, often thought to be one of binary fate decisions, can regulate three different fates is unknown.In order to investigate this process, we used single-cell RNA sequencing to profile progenitors in the embryonic retinas. Using known markers for two of these progenitor classes, we identified all three. This analysis revealed a potential three-tiered model of Notch signaling, with each tier specifying one progenitor class through the regulation of two sequential fate decision points. We provide further evidence for this model using experimental simulation of a middle-level Notch signaling state, and add to our model mechanisms for how this middle state is achieved. This model is further supported with data collected using high-throughput enhancer discovery and analysis techniques that we developed, which also allow for the investigation of upstream transcriptional regulation in other systems.
590 $a School code: 0084.
650 4 $a Developmental biology. $3 592588
650 4 $a Molecular biology. $3 517296
653 $a Development
653 $a Gene regulatory networks
653 $a Notch
653 $a Retina
653 $a Transcriptional regulation
690 $a 0758
690 $a 0307
710 2 $a Harvard University. $b Biology, Molecular and Cellular. $3 2093132
773 0 $t Dissertations Abstracts International $g 82-09B.
790 $a 0084
791 $a Ph.D.
792 $a 2021
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28315811