Crim1 has cell-autonomous and paracrine roles during embryonic heart development

Iyer, Swati, Chou, Fang Yu, Wang, Richard, Chiu, Han Sheng, Raju, Vinay K. Sundar, Little, Melissa H., Thomas, Walter G., Piper, Michael, & Pennisi, David J. (2016) Crim1 has cell-autonomous and paracrine roles during embryonic heart development. Scientific Reports, 6, Article number: 19832.

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The epicardium has a critical role during embryonic development, contributing epicardium-derived lineages to the heart, as well as providing regulatory and trophic signals necessary for myocardial development. Crim1 is a unique trans-membrane protein expressed by epicardial and epicardially-derived cells but its role in cardiogenesis is unknown. Using knockout mouse models, we observe that loss of Crim1 leads to congenital heart defects including epicardial defects and hypoplastic ventricular compact myocardium. Epicardium-restricted deletion of Crim1 results in increased epithelial-to-mesenchymal transition and invasion of the myocardium in vivo, and an increased migration of primary epicardial cells. Furthermore, Crim1 appears to be necessary for the proliferation of epicardium-derived cells (EPDCs) and for their subsequent differentiation into cardiac fibroblasts. It is also required for normal levels of cardiomyocyte proliferation and apoptosis, consistent with a role in regulating epicardium-derived trophic factors that act on the myocardium. Mechanistically, Crim1 may also modulate key developmentally expressed growth factors such as TGFβs, as changes in the downstream effectors phospho-SMAD2 and phospho-ERK1/2 are observed in the absence of Crim1. Collectively, our data demonstrates that Crim1 is essential for cell-autonomous and paracrine aspects of heart development.

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ID Code: 107030
Item Type: Journal Article
Refereed: Yes
DOI: 10.1038/srep19832
ISSN: 2045-2322
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2016 Macmillan Publishers Limited
Copyright Statement: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Deposited On: 17 May 2017 05:57
Last Modified: 18 May 2017 00:38

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