Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes
- Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
- University of Ulm, Germany
- Max Planck Institute for Heart and Lung Research, Germany
Abstract
Mammalian cardiomyocytes become post-mitotic shortly after birth. Understanding how this occurs is highly relevant to cardiac regenerative therapy. Yet, how cardiomyocytes achieve and maintain a post-mitotic state is unknown. Here, we show that cardiomyocyte centrosome integrity is lost shortly after birth. This is coupled with relocalization of various centrosome proteins to the nuclear envelope. Consequently, postnatal cardiomyocytes are unable to undergo ciliogenesis and the nuclear envelope adopts the function as cellular microtubule organizing center. Loss of centrosome integrity is associated with, and can promote, cardiomyocyte G0/G1 cell cycle arrest suggesting that centrosome disassembly is developmentally utilized to achieve the post-mitotic state in mammalian cardiomyocytes. Adult cardiomyocytes of zebrafish and newt, which are able to proliferate, maintain centrosome integrity. Collectively, our data provide a novel mechanism underlying the post-mitotic state of mammalian cardiomyocytes as well as a potential explanation for why zebrafish and newts, but not mammals, can regenerate their heart.
Article and author information
Author details
Reviewing Editor
- Yukiko M Yamashita, University of Michigan, United States
Ethics
Animal experimentation: The investigation conforms with the Guide for the Care and Use of Laboratory Animals published by the Directive 2010/63/EU of the European Parliament and according to the regulations issued by the Committee for Animal Rights Protection of the State of Hessen (Regierungspraesidium Darmstadt) as well as Baden-Württemberg (Regierungspraesidium Tübingen). Extraction of organs and preparation of primary cell cultures were approved by the local Animal Ethics Committee in accordance to governmental and international guidelines on animal experimentation (protocol TS - 5/13 Nephropatho; Zebrafish protocol number o.183).
Version history
- Received: November 11, 2014
- Accepted: July 30, 2015
- Accepted Manuscript published: August 6, 2015 (version 1)
- Version of Record published: August 19, 2015 (version 2)
Copyright
© 2015, Zebrowski et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes
eLife 4:e05563.
https://doi.org/10.7554/eLife.05563
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