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one in heart asymmetry in the inlet path It was not described until now, according to researchers at the National Center for Cardiovascular Research (CNIC), who have created a 3D atlas of the heart formation process in its embryonic stageA powerful tool that can help identify CMO Y Poles Congenital heart malformations occur.

as he highlighted Michael TorresHead of the Genetic Control of Organ Development and Regeneration Group at CNIC and director of the study published in Nature Cardiovascular Research, who explains that this work “will be very helpful in understanding the development of the heart,” and also for the study of formation of other organs and tissues,

A fundamental question in developmental biology, as explained by CNIC researchers, is how tissues acquire Simple geometry to complex shapeA process called morphogenesis.

This function is relatively accessible to organs that develop in a highly reproducible pattern, such as limbs or eyes, and can be easily seen; although it is more difficult in organs such as the heart of mammalsAccording to the CNIC researchers, there is extreme morphological variability and little is accessible to video microscopy.

divergences that converge

Thus the development of the heart presents peculiarities with respect to the characteristic of the formation of other organs. Thus, during early cardiogenesis two embryos are not hearts That they are so similar, so different that it is difficult to determine which is in a more advanced stage of development. Over time, these converge to the previously clearly distinct morphology. generate a typical neonatal heart, explains Torres

The challenge is to capture the average evolution of cardiac tissue geometry from a wide range of natural variability and power. Discrimination between physical morphological variations And unusual from a large enough sample. “Only then we will understand its merits” physical morphogenesis and identify when and how discrepancies occur”, explains this expert.

To create dynamic 3D atlases now presented and overcome limitations in acquiring live images, the CNIC team obtained high-resolution images from an extensive collection of embryonic mouse heart collected during the major stages of their development and with high temporal densities.

In the process, “we realized that the morphology of the heart could not be distinguished from the surrounding tissue, because the construction of the cardiac tube looked the same. geological fold formed in a continuous layer of mesodermthat is, the cell layer that constitutes the embryo of the pericardial cavity”, explains Torres. Therefore, according to the study’s first author, Isaac Stephen“We captured all the tissues of pericardial cavity and the underlying precursor endoderm”.

Next, the researchers converted the images into digital versions and, thanks to a system of morphometric migrationHe arranged them provisionally, since the moment of receiving the embryo does not necessarily correspond to the time of actual morphological development.

CNIC scientists use a recently developed approach: the mapping between surfaceswhich generates maps of corresponding points between similar shapes with sufficient point density to reconstruct the entire surface of the objects.

“This method made it possible to identify similar positions between groups of samples at the same level and at successive stages of development,” says Esteban. So he created a 3D temporal atlas showing Trajectory of cardiac tube formation and local morphological variability at each stage.

initial asymmetry

With this tool, a better quantitative study of the development of an organ can be made, as well as how organs begin to develop. Defects associated with genetic mutation,

“The observations so far in the case of the heart have been qualitative. Now we can develop a quantitative analysiswhich will no longer depend on the researcher’s eyes, and furthermore, with our instrument we have not only studied the global morphology of the heart but also mapped it locally”, emphasizes Torres.

Highlights the importance of knowing the professional New oddity yet unexplained, despite the fact that there are many laboratories that have been studying the development of the heart since the beginning of the last century. CNIC researchers also verified that this abnormality in the flow path of the heart happens too soon,

The authors of this work also analyzed mutant chain in which the already known curvature of the fetal heart to the right was changed and found that the new asymmetry now described was reversed in these images of the mutants, leading to the conclusion that “the now described asymmetry is related to Normal abnormality of the adult heart.

The information obtained by the CNIC team suggests that the areas commonly involved in cardiac malformations coincide with areas of high morphological heterogeneity and/or high variability development time. “This observation suggests that morphological variability may underlie the high natural incidence of congenital cardiac malformations, which affect 1% of live births Stephen assured.

one from here Application Most relevant to this task, “by identifying hotspots of variability that can guide us in this” the place where the related defects occur for malformations”, also taking into account the higher rate of cardiac malformations at birth compared to other organs.

The heart is the first organ to function in embryonic development. begins to pump blood very quickly and the rapid transition from a stage of undifferentiated precursors to an active organ, which already requires a certain architectural configuration, is accompanied by the development of very drastic changes in a very short period of time, this Could explain the high index. of distortions.

The generated methodology can be applied for quantitative analysis of the morphology of any organ or organelles.

According to Torres, the main limitation of the study is the use of fixed images to reconstruct a dynamic process, which does not allow the analysis of the cellular underpinnings of tissue deformation. However, the generated atlas will be an essential basis for contributing to this knowledge and scientists are already working on incorporating cellular data into this new dynamic atlas of heart development.

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