Dissecting genes and signals controlling pancreatic islet morphogenesis and differentiation
Abstract/Contents
- Abstract
- The pancreas is a mixed endocrine and exocrine organ associated with the digestive tract. Pancreatic islets are spheroid endocrine micro-organs dispersed throughout the pancreas which secrete hormones into the bloodstream, whereas acinar and ductal cells form a branched epithelial network which transmits digestive enzymes into the intestine. During development, islets, ducts, and acinar cells originate from common progenitors. Islet cells begin to differentiate, exit the ductal epithelium, migrate outward, and cluster to form islets. Genes and signals controlling islet cell differentiation and islet morphogenesis in space, time, and lineage remain to be discovered. Additionally, whether the functions of genes and signals characterized in model organisms are conserved in human pancreas biology is frequently difficult to assess. This thesis presents findings and methods that advance knowledge of mechanisms of islet morphogenesis and differentiation at the cellular and tissue levels. In Chapter 2, we address discordance between mouse and human mutant phenotypes by assessing the functional consequences of human gene mutations associated with clinical disease. In Chapter 3, we define a radial axis in islet morphogenesis encoded by the Semaphorin signaling through Neuropilin receptors. In Chapter 4, we identify the transcriptional corepressor ETO as a regulator of islet progenitor development, and in Chapter 5, we develop tools for genetically labeling human α cells. Along with these findings, we describe methods for single-cell resolution live imaging of developing islet cells, somatic delivery of transgenes to intact developing pancreatic tissue cultured ex vivo, and whole-organ high resolution confocal imaging. Overall, the work here contributes to the study of pancreas organogenesis, defining genes and signals that act at regulatory points in development to enable the formation of pancreatic islets.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Pauerstein, Philip Thomas | |
|---|---|---|
| Associated with | Stanford University, Department of Developmental Biology. | |
| Primary advisor | Kim, Seung K | |
| Thesis advisor | Kim, Seung K | |
| Thesis advisor | Kingsley, David M. (David Mark) | |
| Thesis advisor | Krasnow, Mark, 1956- | |
| Thesis advisor | Talbot, William | |
| Advisor | Kingsley, David M. (David Mark) | |
| Advisor | Krasnow, Mark, 1956- | |
| Advisor | Talbot, William |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Philip Thomas Pauerstein. |
|---|---|
| Note | Submitted to the Department of Developmental Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Philip Thomas Pauerstein
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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