Journal article
Crim1 has cell-autonomous and paracrine roles during embryonic heart development
S Iyer, FY Chou, R Wang, HS Chiu, VKS Raju, MH Little, WG Thomas, M Piper, DJ Pennisi
Scientific Reports | Published : 2016
DOI: 10.1038/srep19832
Abstract
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 epicar..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was funded by grants from the National Health and Medical Research Council (NHMRC) to DJP (631658), MP (1057751), MHL (301056 and 455972). MHL is a Senior Principal Research Fellow of the NHMRC, and MP holds an Australian Research Council Future Fellowship (FT120100170). SI was supported by a UQ Research Scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to Professor Richard Harvey for providing us with the Mlc2v-Cre and WT1-CreERT2 mouse lines. We thank Dr. Tracey Harvey and Dr. Aaron Smith for helpful discussions, Ms. Sabrina Oishi for assistance with bright field microscopy and Mr. Lachlan Harris for advice on statistical analyses. We thank the staff of UQBR animal facilities and The Centre for Microscopy and Microanalysis at The University of Queensland for support.