Skip to main content
Duke University Libraries
DukeSpace Scholarship by Duke Authors
  • Login
  • Ask
  • Menu
  • Login
  • Ask a Librarian
  • Search & Find
  • Using the Library
  • Research Support
  • Course Support
  • Libraries
  • About
View Item 
  •   DukeSpace
  • Theses and Dissertations
  • Duke Dissertations
  • View Item
  •   DukeSpace
  • Theses and Dissertations
  • Duke Dissertations
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Mechanisms that drive cardiomyocyte proliferation during zebrafish heart regeneration

Thumbnail
View / Download
78.8 Mb
Date
2014
Author
Gemberling, Matthew P.
Advisor
Poss, Kenneth D
Repository Usage Stats
333
views
92
downloads
Abstract

Heart disease is the leading cause of death in the developed world. Adult mammals cannot replace lost cardiac tissue after injury, leading to reduced quality of life and increased instances of future cardiac issues. Zebrafish possess the ability to regenerate lost cardiac muscle after injury. Upon injury, the zebrafish heart responds in a coordinated fashion resulting in activation of the epicardium and endocardium, cardiomyocyte proliferation, and subsequent vascularization and innervation of the newly formed muscle. Thus zebrafish represent an ideal genetic model to dissect the mechanisms of heart regeneration. Previously, it was discovered that regulatory sequences of the cardiac transcription factor, gata4, become active in the ventricular wall following injury and that these gata4+ cardiomyocytes proliferate and contribute the majority of new muscle to the regenerate. We uncovered that gata4 function is required for cardiomyocyte proliferation and regeneration after injury. Cardiomyocyte proliferation is required to achieve proper regeneration and lack of cardiomyocyte proliferation is a hallmark of failed regeneration in the mammalian system. Therefore, understanding the signals that induce mature cardiomyocyte division is of great scientific and clinical relevance. Utilizing transgenic approaches, we have found that gata4 function and Nrg1 signaling are critical regulators of cardiomyocyte proliferation. We found that Nrg1 was expressed following injury in the zebrafish heart and that inhibition of nrg1-erbb signaling blunted cardiomyocyte proliferation. Using transgenic over-expression of Nrg1, we found that Nrg1 was capable of increasing injury-induced cardiomyocyte proliferation. Furthermore we found that activation of Nrg1 in the uninjured adult heart induces cardiomyocyte proliferation and hallmarks of the regenerative program. Long-term nrg1 expression leads to patterned hyperplastic expansion of the zebrafish ventricle. To our knowledge, this is the first description of a single factor that is sufficient to induce such a dramatic hyperplastic response in an adult heart.

Type
Dissertation
Department
Cell Biology
Subject
Cellular biology
Permalink
https://hdl.handle.net/10161/9412
Citation
Gemberling, Matthew P. (2014). Mechanisms that drive cardiomyocyte proliferation during zebrafish heart regeneration. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/9412.
Collections
  • Duke Dissertations
More Info
Show full item record
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.

Rights for Collection: Duke Dissertations


Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info

Make Your Work Available Here

How to Deposit

Browse

All of DukeSpaceCommunities & CollectionsAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit DateThis CollectionAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit Date

My Account

LoginRegister

Statistics

View Usage Statistics
Duke University Libraries

Contact Us

411 Chapel Drive
Durham, NC 27708
(919) 660-5870
Perkins Library Service Desk

Digital Repositories at Duke

  • Report a problem with the repositories
  • About digital repositories at Duke
  • Accessibility Policy
  • Deaccession and DMCA Takedown Policy

TwitterFacebookYouTubeFlickrInstagramBlogs

Sign Up for Our Newsletter
  • Re-use & Attribution / Privacy
  • Harmful Language Statement
  • Support the Libraries
Duke University