TY - JOUR A1 - Haack, Timm A1 - Abdelilah-Seyfried, Salim T1 - The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis JF - Development : Company of Biologists N2 - Endocardial cells are cardiac endothelial cells that line the interior of the heart tube. Historically, their contribution to cardiac development has mainly been considered from a morphological perspective. However, recent studies have begun to define novel instructive roles of the endocardium, as a sensor and signal transducer of biophysical forces induced by blood flow, and as an angiocrine signalling centre that is involved in myocardial cellular morphogenesis, regeneration and reprogramming. In this Review, we discuss how the endocardium develops, how endocardial-myocardial interactions influence the developing embryonic heart, and how the dysregulation of blood flowresponsive endocardial signalling can result in pathophysiological changes. KW - Endocardium KW - Cardiac development KW - Hemodynamics KW - Bmp KW - Kruppel-like factor 2 KW - Vegf KW - Mechanotransduction KW - Zebrafish KW - Mouse Y1 - 2016 U6 - https://doi.org/10.1242/dev.131425 SN - 0950-1991 SN - 1477-9129 VL - 143 SP - 373 EP - 386 PB - Company of Biologists Limited CY - Cambridge ER - TY - JOUR A1 - Palma-Vera, Sergio E. A1 - Reyer, Henry A1 - Langhammer, Martina A1 - Reinsch, Norbert A1 - Derezanin, Lorena A1 - Fickel, Jörns A1 - Qanbari, Saber A1 - Weitzel, Joachim M. A1 - Franzenburg, Soeren A1 - Hemmrich-Stanisak, Georg A1 - Schön, Jennifer T1 - Genomic characterization of the world's longest selection experiment in mouse reveals the complexity of polygenic traits JF - BMC Biology N2 - Background Long-term selection experiments are a powerful tool to understand the genetic background of complex traits. The longest of such experiments has been conducted in the Research Institute for Farm Animal Biology (FBN), generating extreme mouse lines with increased fertility, body mass, protein mass and endurance. For >140 generations, these lines have been maintained alongside an unselected control line, representing a valuable resource for understanding the genetic basis of polygenic traits. However, their history and genomes have not been reported in a comprehensive manner yet. Therefore, the aim of this study is to provide a summary of the breeding history and phenotypic traits of these lines along with their genomic characteristics. We further attempt to decipher the effects of the observed line-specific patterns of genetic variation on each of the selected traits. Results Over the course of >140 generations, selection on the control line has given rise to two extremely fertile lines (>20 pups per litter each), two giant growth lines (one lean, one obese) and one long-distance running line. Whole genome sequencing analysis on 25 animals per line revealed line-specific patterns of genetic variation among lines, as well as high levels of homozygosity within lines. This high degree of distinctiveness results from the combined effects of long-term continuous selection, genetic drift, population bottleneck and isolation. Detection of line-specific patterns of genetic differentiation and structural variation revealed multiple candidate genes behind the improvement of the selected traits. Conclusions The genomes of the Dummerstorf trait-selected mouse lines display distinct patterns of genomic variation harbouring multiple trait-relevant genes. Low levels of within-line genetic diversity indicate that many of the beneficial alleles have arrived to fixation alongside with neutral alleles. This study represents the first step in deciphering the influence of selection and neutral evolutionary forces on the genomes of these extreme mouse lines and depicts the genetic complexity underlying polygenic traits. KW - Mouse KW - Fertility KW - Body mass KW - Endurance KW - Selective breeding KW - Genetic KW - drift KW - Bottleneck KW - Whole genome sequencing KW - Single-nucleotide KW - polymorphism KW - Structural variation Y1 - 2022 U6 - https://doi.org/10.1186/s12915-022-01248-9 SN - 1741-7007 VL - 20 IS - 1 PB - BMC CY - London ER -