Proper heart morphogenesis requires a delicate balance between hemodynamic forces, myocardial activity, morphogen gradients, and epigenetic signaling, all of which are coupled with genetic regulatory networks. Recently both in vivo and in silico studies have tried to better understand hemodynamics at varying stages of veretebrate cardiogenesis. In particular, the intracardial hemodynamics during the onset of trabeculation is notably complex-the inertial and viscous fluid forces are approximately equal at this stage and small perturbations in morphology, scale, and steadiness of the flow can lead to significant changes in bulk flow structures, shear stress distributions, and chemical morphogen gradients. The immersed boundary method was used to numerically simulate fluid flow through simplified two-dimensional and stationary trabeculated ventricles of 72, 80, and 120 h post fertilization zebrafish embryos and -inhibited embryos at seven days post fertilization. A 2D idealized trabeculated ventricular model was also used to map the bifurcations in flow structure that occur as a result of the unsteadiness of flow, trabeculae height, and fluid scale ( R e ). Vortex formation occurred in intertrabecular regions for biologically relevant parameter spaces, wherein flow velocities increased. This indicates that trabecular morphology may alter intracardial flow patterns and hence ventricular shear stresses and morphogen gradients. A potential implication of this work is that the onset of vortical (disturbed) flows can upregulate Notch1 expression in endothelial cells in vivo and hence impacts chamber morphogenesis, valvulogenesis, and the formation of the trabeculae themselves. Our results also highlight the sensitivity of cardiac flow patterns to changes in morphology and blood rheology, motivating efforts to obtain spatially and temporally resolved chamber geometries and kinematics as well as the careful measurement of the embryonic blood rheology. The results also suggest that there may be significant changes in shear signalling due to morphological and mechanical variation across individuals and species.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463151 | PMC |
http://dx.doi.org/10.3390/jcdd6010006 | DOI Listing |
Bull Math Biol
January 2025
School of Mathematics, University of Minnesota, Minneapolis, USA.
Spatial distributions of morphogens provide positional information in developing systems, but how the distributions are established and maintained remains an open problem. Transport by diffusion has been the traditional mechanism, but recent experimental work has shown that cells can also communicate by filopodia-like structures called cytonemes that make direct cell-to-cell contacts. Here we investigate the roles each may play individually in a complex tissue and how they can jointly establish a reliable spatial distribution of a morphogen.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA.
Transcription factors (TFs) regulate gene expression despite constraints from chromatin structure and the cell cycle. Here we examine the concentration-dependent regulation of by the Bicoid morphogen through a combination of quantitative imaging, mathematical modeling and epigenomics in embryos. By live imaging of MS2 reporters, we find that, following mitosis, the timing of transcriptional activation driven by the P2 ( P2) enhancer directly reflects Bicoid concentration.
View Article and Find Full Text PDFCell
December 2024
Cell Design Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:
In vitro development relies primarily on treating progenitor cells with media-borne morphogens and thus lacks native-like spatial information. Here, we engineer morphogen-secreting organizer cells programmed to self-assemble, via cell adhesion, around mouse embryonic stem (ES) cells in defined architectures. By inducing the morphogen WNT3A and its antagonist DKK1 from organizer cells, we generated diverse morphogen gradients, varying in range and steepness.
View Article and Find Full Text PDFBiophys J
December 2024
CRTD - Center for Regenerative Therapies TU Dresden, Dresden, Germany; PoL - Excellence Cluster Physics of Life, Dresden, Germany. Electronic address:
Embryonic development is orchestrated by the action of morphogens, which spread out from a local source and activate, in a field of target cells, different cellular programs based on their concentration gradient. Fibroblast growth factor 8 (Fgf8) is a morphogen with important functions in embryonic organizing centers. It forms a gradient in the extracellular space by free diffusion, interaction with the extracellular matrix (ECM), and receptor-mediated endocytosis.
View Article and Find Full Text PDFJ R Soc Interface
December 2024
Department of Mathematics, University College London, London WC1E 6BT, UK.
In developing embryos, cells acquire distinct identities depending on their position in a tissue. Secreted signalling molecules, known as morphogens, act as long-range cues to provide the spatial information that controls these cell fate decisions. In several tissues, both the level and the duration of morphogen signalling appear to be important for determining cell fates.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!