Search

That the highly trabeculated ventricular walls of the developing embryos transform to the arrangement during the fetal stages, when the mural architecture is dominated by the thickness of the compact myocardium, has been explained by the coalescence of trabeculations, often erroneously described as 'compaction'. Recent data, however, support differential rates of growth of the trabecular and compact layers as the major driver of change. Here, these processes were assessed quantitatively and visualized in standardized views. We used a larger dataset than has previously been available of mouse hearts, covering the period from embryonic day 10.5 to postnatal day 3, supported by images from human hearts. The volume of the trabecular layer increased throughout development, in contrast to what would be expected had there been 'compaction'. During the transition from embryonic to fetal life, the rapid growth of the compact layer diminished the proportion of trabeculations. Similarly, great expansion of the central cavity reduced the proportion of the total cavity made up of intertrabecular recesses. Illustrations of the hearts with the median value of left ventricular trabeculation confirm a pronounced growth of the compact wall, with prominence of the central cavity. This corresponds, in morphological terms, to a reduction in the extent of the trabecular layer. Similar observations were made in the human hearts. We conclude that it is a period of comparatively slow growth of the trabecular layer, rather than so‐called compaction, that is the major determinant of the changing morphology of the ventricular walls of both mouse and human hearts. [ABSTRACT FROM AUTHOR]

The separation of the outflow tract of the developing heart into the systemic and pulmonary arterial channels remains controversial and poorly understood. The definitive outflow tracts have three components. The developing outflow tract, in contrast, has usually been described in two parts. When the tract has exclusively myocardial walls, such bipartite description is justified, with an obvious dogleg bend separating proximal and distal components. With the addition of non‐myocardial walls distally, it becomes possible to recognise three parts. The middle part, which initially still has myocardial walls, contains within its lumen a pair of intercalated valvar swellings. The swellings interdigitate with the distal ends of major outflow cushions, formed by the remodelling of cardiac jelly, to form the primordiums of the arterial roots. The proximal parts of the major cushions, occupying the proximal part of the outflow tract, which also has myocardial walls, themselves fuse and muscularise. The myocardial shelf thus formed remodels to become the free‐standing subpulmonary infundibulum. Details of all these processes are currently lacking. In this account, we describe the anatomical changes seen during the overall remodelling. Our interpretations are based on the interrogation of serially sectioned histological and high‐resolution episcopic microscopy datasets prepared from developing human and mouse embryos, with some of the datasets processed and reconstructed to reveal the specific nature of the tissues contributing to the separation of the outflow channels. Our findings confirm that the tripartite postnatal arrangement can be correlated with the changes occurring during development. [ABSTRACT FROM AUTHOR]

Controversies continue regarding several aspects of the anatomy of the morphologically right ventricle. There is disagreement as to whether the ventricle should be assessed in bipartite or tripartite fashion, and the number of leaflets to be found in the tricuspid valve. In particular, there is no agreement as to whether a muscular outlet septum is present in the normally constructed heart, nor how many septal components are to be found during normal development. Resolving these issues is of potential significance to those investigating and treating children with congenitally malformed hearts. With all these issues in mind, we have revisited our own experience in investigating the development and morphology of the normal right ventricle. To assess development, we have examined a large number of datasets, prepared by both standard and episcopic microscopy, from human and murine embryos. In terms of gross anatomy, we have compared dissections of normal autopsied hearts with virtual dissections of datasets prepared using computed tomography. Our developmental and postnatal studies, taken together, confirm that the ventricle is best assessed in tripartite fashion, with the three parts representing its inlet, apical trabecular, and outlet components. The ventricular septum, however, has only muscular and membranous components. The muscular part incorporates a small component derived from the muscularised fused proximal outflow cushions, but this part cannot be distinguished from the much larger part that is incorporated within the free‐standing muscular infundibular sleeve. We confirm that the tricuspid valve itself has three components, which are located inferiorly, septally, and antero‐superiorly. [ABSTRACT FROM AUTHOR]

Large-scale phenotyping efforts have demonstrated that approximately 2530% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.514.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation., Author(s): Vicente Perez-Garcia [1, 2]; Elena Fineberg [1, 2]; Robert Wilson [3]; Alexander Murray [1, 2]; Cecilia Icoresi Mazzeo [4]; Catherine Tudor [4]; Arnold Sienerth [1, 2]; Jacqueline K. White [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.09.019 Byline: Anita Abu-Daya (a), Amy K. Sater (b), Dan E. Wells (b), Timothy J. Mohun (a), Lyle B. Zimmerman (a) Keywords: Xenopus tropicalis; Mutation; Heart; Cardiac; myh6; Valve; Trabeculation; Sarcomere; Myosin; Genetic mapping Abstract: Mechanisms coupling heart function and cardiac morphogenesis can be accessed in lower vertebrate embryos that can survive to swimming tadpole stages on diffused oxygen. Forward genetic screens in Xenopus tropicalis have identified more than 80 mutations affecting diverse developmental processes, including cardiac morphogenesis and function. In the first positional cloning of a mutation in X. tropicalis, we show that non-contractile hearts in muzak (muz) embryos are caused by a premature stop codon in the cardiac myosin heavy chain gene myh6. The mutation deletes the coiled-coil domain responsible for polymerization into thick filaments, severely disrupting the cardiomyocyte cytoskeleton. Despite the lack of contractile activity and absence of a major structural protein, early stages of cardiac morphogenesis including looping and chamber formation are grossly normal. Muz hearts subsequently develop dilated chambers with compressed endocardium and fail to form identifiable cardiac valves and trabeculae. Author Affiliation: (a) MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK (b) Department of Biology and Biochemistry, University of Houston, Houston TX, USA Article History: Received 30 April 2009; Revised 17 August 2009; Accepted 14 September 2009