Logan-Graf, Gregory
(2017)
Genetic and Environmental Factors that Control Merkel Cell Development and Survival.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Merkel cells are mechanosensory cells that detect light-touch stimuli including shape, texture, and size. Merkel cells are derived from the epidermis, are innervated by SAI neurons, and require the transcription factor Atoh1 for their development. In this dissertation, we aim to identify genetic and environmental factors that promote Merkel cell production during embryogenesis and adulthood. First, we interrogated the role of Notch signaling during Merkel cell development by manipulating elements of the Notch signaling pathway in transgenic mice. We found that canonical Notch signaling inhibits Merkel cell specification during embryogenesis. Second, we used a live animal imaging technique to track how touch domes change over time as well as how long Merkel cells survive in adult mice. We found that Merkel cells persist for longer than previously thought. Third, we used a live imaging technique to visualize the interaction between SAI neurons and Merkel cells, and found that direct contact from SAI neurons is not required for Merkel cell production. Finally, we tested how skin abrasions affect Merkel cell number, and we found that skin abrasions decrease Merkel cell number in hairless mice, but not hairy mice; suggesting the hair follicle is required to restore or maintain Merkel cell number after injury. Together these findings give insight into how Merkel cells develop and how they are replaced in adult mice. Understanding the environmental and genetic factors that promote Merkel cell development can be helpful for studying Merkel cell carcinoma, a rare but deadly cancer which is derived from skin progenitors and shares characteristics of Merkel cells.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
7 July 2017 |
| Date Type: |
Publication |
| Defense Date: |
5 June 2017 |
| Approval Date: |
7 July 2017 |
| Submission Date: |
6 July 2017 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
156 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Cellular and Molecular Pathology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Development, Merkel cells, Somatosensation |
| Date Deposited: |
07 Jul 2017 13:36 |
| Last Modified: |
07 Jul 2017 13:36 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/32705 |
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