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Interplay of cell–cell contacts and RhoA/ MRTF ‐A signaling regulates cardiomyocyte identity
Author(s) -
Dorn Tatjana,
Kornherr Jessica,
Parrotta Elvira I,
Zawada Dorota,
Ayetey Harold,
Santamaria Gianluca,
Iop Laura,
Mastantuono Elisa,
Sinnecker Daniel,
Goedel Alexander,
Dirschinger Ralf J,
My Ilaria,
Laue Svenja,
Bozoglu Tarik,
Baarlink Christian,
Ziegler Tilman,
Graf Elisabeth,
Hinkel Rabea,
Cuda Giovanni,
Kääb Stefan,
Grace Andrew A,
Grosse Robert,
Kupatt Christian,
Meitinger Thomas,
Smith Austin G,
Laugwitz KarlLudwig,
Moretti Alessandra
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798133
Subject(s) - biology , microbiology and biotechnology , rhoa , cell fate determination , adipogenesis , progenitor cell , actin cytoskeleton , cellular differentiation , cell , transcription factor , signal transduction , actin , cytoskeleton , stem cell , genetics , gene , mesenchymal stem cell
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.