title: Morphogenesis of myocardial trabeculae in the mouse embryo.
abstract: Formation of trabeculae in the embryonic heart and the remodelling that occurs prior to birth is a conspicuous, but poorly understood, feature of vertebrate cardiogenesis. Mutations disrupting trabecular development in the mouse are frequently embryonic lethal, testifying to the importance of the trabeculae, and aberrant trabecular structure is associated with several human cardiac pathologies. Here, trabecular architecture in the developing mouse embryo has been analysed using high-resolution episcopic microscopy (HREM) and three-dimensional (3D) modelling. This study shows that at all stages from mid-gestation to birth, the ventricular trabeculae comprise a complex meshwork of myocardial strands. Such an arrangement defies conventional methods of measurement, and an approach based upon fractal algorithms has been used to provide an objective measure of trabecular complexity. The extent of trabeculation as it changes along the length of left and right ventricles has been quantified, and the changes that occur from formation of the four-chambered heart until shortly before birth have been mapped. This approach not only measures qualitative features evident from visual inspection of 3D models, but also detects subtle, consistent and regionally localised differences that distinguish each ventricle and its developmental stage. Finally, the combination of HREM imaging and fractal analysis has been applied to analyse changes in embryonic heart structure in a genetic mouse model in which trabeculation is deranged. It is shown that myocardial deletion of the Notch pathway component Mib1 (Mib1(flox/flox) ; cTnT-cre) results in a complex array of abnormalities affecting trabeculae and other parts of the heart.
authors.affiliation: Institute of Cardiovascular Science, University College London, London, UK.|The Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Captur
authors.affiliation: The Francis Crick Institute Mill Hill Laboratory, The Ridgeway, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
authors.affiliation: The Francis Crick Institute Mill Hill Laboratory, The Ridgeway, London, UK.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Bennett
authors.affiliation: Intercellular Signalling in Cardiovascular Development & Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Luxán
authors.affiliation: Monash Cardiovascular Research Centre, MonashHEART, Monash University, Clayton, Australia.
authors.forename: Arthur
authors.initials: A
authors.lastname: Nasis
authors.affiliation: Intercellular Signalling in Cardiovascular Development & Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: de la Pompa
authors.affiliation: Institute of Cardiovascular Science, University College London, London, UK.|The Barts Heart Centre, Barts Health NHS Trust, London, UK.
authors.forename: James C
authors.initials: JC
authors.lastname: Moon
authors.affiliation: The Francis Crick Institute Mill Hill Laboratory, The Ridgeway, London, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mohun
mesh_terms: D000818:Animals; D006321:Heart / Q000196:embryology*; D051379:Mice / Q000196:embryology*; D009206:Myocardium; D038081:Organogenesis
keywords: cardiac embryology; cardiogenesis; developmental biology; non-compaction cardiomyopathy