Interplay of cell–cell contacts and RhoA/MRTF-A signaling regulates cardiomyocyte identity

Dorn T, Kornherr J, Parrotta EI, Zawada D, Ayetey H, Santamaria G, Iop L, Mastantuono E, Sinnecker D, Goedel A, Dirschinger RJ, My I, Laue S, Bozoglu T, Baarlink C, Ziegler T, Graf E, Hinkel R, Cuda G, Kaeaeb S, Grace AA, Grosse R, Kupatt C, Meitinger T, Smith AG, Laugwitz KL, Moretti A (2018)

Publication Type: Journal article

Publication year: 2018

Journal

EMBO Journal EMBO Press

Book Volume: 37

Article Number: e98133

Journal Issue: 12

DOI: 10.15252/embj.201798133

Abstract

Cell–cell and cell–matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell–cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA-ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis-inducing signals. We also demonstrate by in vivo fate mapping and clonal analysis of cardiac progenitors that cardiac fat and a subset of cardiac muscle arise from a common precursor expressing Isl1 and Wt1 during heart development, suggesting related mechanisms of determination between the two lineages.

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) University of Cambridge GB United Kingdom (GB) Magna Græcia University of Catanzaro / Università degli studi Magna Græcia di Catanzaro IT Italy (IT) Philipps-Universität Marburg DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Royal Papworth Hospital NHS Foundation Trust GB United Kingdom (GB)

How to cite

APA:

Dorn, T., Kornherr, J., Parrotta, E.I., Zawada, D., Ayetey, H., Santamaria, G.,... Moretti, A. (2018). Interplay of cell–cell contacts and RhoA/MRTF-A signaling regulates cardiomyocyte identity. EMBO Journal, 37(12). https://doi.org/10.15252/embj.201798133

MLA:

Dorn, Tatjana, et al. "Interplay of cell–cell contacts and RhoA/MRTF-A signaling regulates cardiomyocyte identity." EMBO Journal 37.12 (2018).

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