title: N-cadherin relocalization during cardiac trabeculation.
abstract: During cardiac trabeculation, cardiomyocytes delaminate from the outermost (compact) layer to form complex muscular structures known as trabeculae. As these cardiomyocytes delaminate, the remodeling of adhesion junctions must be tightly coordinated so cells can extrude from the compact layer while remaining in tight contact with their neighbors. In this study, we examined the distribution of N-cadherin (Cdh2) during cardiac trabeculation in zebrafish. By analyzing the localization of a Cdh2-EGFP fusion protein expressed under the control of the zebrafish cdh2 promoter, we initially observed Cdh2-EGFP expression along the lateral sides of embryonic cardiomyocytes, in an evenly distributed pattern, and with the occasional appearance of punctae. Within a few hours, Cdh2-EGFP distribution on the lateral sides of cardiomyocytes evolves into a clear punctate pattern as Cdh2-EGFP molecules outside the punctae cluster to increase the size of these aggregates. In addition, Cdh2-EGFP molecules also appear on the basal side of cardiomyocytes that remain in the compact layer. Delaminating cardiomyocytes accumulate Cdh2-EGFP on the surface facing the basal side of compact layer cardiomyocytes, thereby allowing tight adhesion between these layers. Importantly, we find that blood flow/cardiac contractility is required for the transition from an even distribution of Cdh2-EGFP to the formation of punctae. Furthermore, using time-lapse imaging of beating hearts in conjunction with a Cdh2 tandem fluorescent protein timer transgenic line, we observed that Cdh2-EGFP molecules appear to move from the lateral to the basal side of cardiomyocytes along the cell membrane, and that Erb-b2 receptor tyrosine kinase 2 (Erbb2) function is required for this relocalization.
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Anoop V
authors.initials: AV
authors.lastname: Cherian
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Fukuda
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Sruthy Maria
authors.initials: SM
authors.lastname: Augustine
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Maischein
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany didier.stainier@mpi-bn.mpg.de.
authors.forename: Didier Y R
authors.initials: DY
authors.lastname: Stainier
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015820:Cadherins / Q000378:metabolism*; D003326:Coronary Circulation; D049452:Green Fluorescent Proteins; D006321:Heart / Q000196:embryology*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D015820:Cadherins; D049452:Green Fluorescent Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D029961:Zebrafish Proteins; C000605819:Cdh2 protein, zebrafish; C485184:enhanced green fluorescent protein
keywords: Cdh2-EGFP; Erbb2 signaling; N-cadherin; heart development; trabeculation