The activity of mouse Cerberus like 2 during cardiogenesis - genetic and morphogenetic studies

Cardiogenesis is a delicate and complex process that requires the coordination of an intricate network of pathways and the different cell types. Therefore, understanding heart development at the morphogenetic level is an essential requirement to uncover the causes of congenital heart disease and to provide insight for disease therapies. Mouse Cerberus like 2 (Cerl2) has been defined as a Nodal antagonist in the node with an important role in the Left-Right (L/R) axis establishment, at the early embryonic development. As expected, Cerl2 knockout mice (Cerl2-/-) showed multiple laterality defects with associated cardiac failure. In order to identify the endogenous role of Cerl2 during heart formation independent of its described functions in the node, we accurately analyzed animals where laterality defects were not present. We thereby unravel the consequences of Cerl2 lossof- function in the heart, namely increased left ventricular thickness due to hyperplasia of cardiomyocytes and de-regulated expression of cardiac genes. Furthermore, the Cerl2 mutant neonates present impaired cardiac function. Once that the cardiac expression of Cerl2 is mostly observed in the left ventricle until around midgestration, this result suggest a specific regulatory role of Cerl2 during the formation of the left ventricular myoarchitecture. Here, we present two possible molecular mechanisms underlying the cardiac Cerl2 function, the regulation of Cerl2 antagonist in activation of the TGFßs/Nodal/Activin/Smad2 signaling identified by increased Smad2 phosphorilation in Cerl2-/- hearts and the negative feedback between Cerl2 and Wnt/ß-catenin signaling in heart formation. In this work and since embryonic stem cells derived from 129 mice strain is extensively used to produce targeted mutants, we also present echocardiographic reference values to progressive use of juveniles and young adult 129/Sv strain in cardiac studies. In addition, we investigate the cardiac physiology of the surviving Cerl2 mutants in 129/Sv background over time through a follow-up study using echocardiographic analysis. Our results revealed that Cerl2-/- mice are able to improve and maintain the diastolic and most of systolic cardiac physiologic parameters as analyzed until young adult age. Since Cerl2 is no longer expressed in the postnatal heart, we suggest that an intrinsic and compensatory mechanism of adaptation may be active for recovering the decreased cardiac function found in Cerl2 mutant neonates. Altogether, these data highlight the role of Cerl2 during embryonic heart development in mice. Furthermore, we also suggest that Cerl2-/- may be an interesting model to uncover the molecular, cellular and physiological mechanisms behind the improvement of the cardiac function, contributing to the development of therapeutic approaches to treat heart failures.

Population structure of the black seabream Spondyliosoma cantharus along the south-west Portuguese coast inferred from otolith chemistry

The chemistry of black seabream Spondyliosoma cantharus otoliths from three main fishery grounds (Olhao, Sagres and Sesimbra) located along c. 400 km of the Portuguese south and west coasts was examined. Element:Ca ratios were determined in whole otoliths and otolith cores of young adult specimens of 23 years of age. Using the data from whole otoliths, it was possible to discriminate among S. cantharus from the three fishing grounds with an average accuracy of 91%. Differences among fishing grounds were significant for all element:Ca ratios, and otoliths from Sagres had significantly higher levels of all ratios compared to the other fishing grounds. In contrast, the chemical composition of the otolith core, representative of the larval stage, showed limited variation among the fishing grounds, with an average discrimination accuracy of only 44%, although the Mg:Ca ratio of the otolith cores was also significantly higher for the Sagres samples. The data suggest that larval stages experienced a homogenous environment consistent with an offshore oceanic spawning. Juveniles appeared to display local residency on the inshore fishing grounds, areas probably characterized by greater environmental heterogeneity. Spondyliosoma cantharus population structure is consistent with distinct local population units that share a spawning ground providing recruits to different coastal fishery areas.