title: In Vivo Visualization of Cardiomyocyte Apicobasal Polarity Reveals Epithelial to Mesenchymal-like Transition during Cardiac Trabeculation.
abstract: Despite great strides in understanding cardiac trabeculation, many mechanistic aspects remain unclear. To elucidate how cardiomyocyte shape changes are regulated during this process, we engineered transgenes to label their apical and basolateral membranes. Using these tools, we observed that compact-layer cardiomyocytes are clearly polarized while delaminating cardiomyocytes have lost their polarity. The apical transgene also enabled the imaging of cardiomyocyte apical constriction in real time. Furthermore, we found that Neuregulin signaling and blood flow/cardiac contractility are required for cardiomyocyte apical constriction and depolarization. Notably, we observed the activation of Notch signaling in cardiomyocytes adjacent to those undergoing apical constriction, and we showed that this activation is positively regulated by Neuregulin signaling. Inhibition of Notch signaling did not increase the percentage of cardiomyocytes undergoing apical constriction or of trabecular cardiomyocytes. These studies provide information about cardiomyocyte polarization and enhance our understanding of the complex mechanisms underlying ventricular morphogenesis and maturation.
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Jiménez-Amilburu
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: S Javad
authors.initials: SJ
authors.lastname: Rasouli
authors.affiliation: Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Staudt
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Chiba
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: didier.stainier@mpi-bn.mpg.de.
authors.forename: Didier Y R
authors.initials: DYR
authors.lastname: Stainier
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D016764:Cell Polarity / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D057054:Molecular Imaging; D009024:Morphogenesis / Q000235:genetics; D009200:Myocardial Contraction / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D020890:Neuregulin-1 / Q000235:genetics*; D038081:Organogenesis / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics; D015398:Signal Transduction; D019076:Transgenes; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D020890:Neuregulin-1; D051880:Receptors, Notch; D029961:Zebrafish Proteins
keywords: EMT; apical constriction; apicobasal polarity; cardiomyocyte depolarization; live imaging; trabeculation; zebrafish