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BACKGROUND Proper development of the great vessels of the heart and septation of the cardiac outflow tract requires cardiac neural crest cells. These cells give rise to the parasympathetic cardiac ganglia, the smooth muscle layer of the great vessels, some cardiomyocytes, and the conotruncal cushions and aorticopulmonary septum of the outflow tract. Ablation of cardiac neural crest cells results in defective patterning of each of these structures. Previous studies have shown that targeted deletion of the forkhead transcription factor C2 (Foxc2), results in cardiac phenotypes similar to that derived from cardiac neural crest cell ablation. RESULTS We report that Foxc2-/- embryos on the 129s6/SvEv inbred genetic background display persistent truncus arteriosus and hypoplastic ventricles before embryonic lethality. Foxc2 loss-of-function resulted in perturbed cardiac neural crest cell migration and their reduced contribution to the outflow tract as evidenced by lineage tracing analyses together with perturbed expression of the neural crest cell markers Sox10 and Crabp1. Foxc2 loss-of-function also resulted in alterations in PlexinD1, Twist1, PECAM1, and Hand1/2 expression in association with vascular and ventricular defects. CONCLUSIONS Our data indicate Foxc2 is required for proper migration of cardiac neural crest cells, septation of the outflow tract, and development of the ventricles. Developmental Dynamics 247:1286-1296, 2018. © 2018 Wiley Periodicals, Inc.

The placenta is an essential organ that mediates interaction between maternal and fetal circulatory systems. The placenta is absolutely required for pregnancy and fetal growth, and placental disorders are associated with adverse maternal and fetal clinical outcomes. Placental calcification is characterized by calcium-phosphate mineral deposits in placental tissue, and placental calcification has been reported in association with adverse maternal and fetal clinical outcomes, including preterm birth, preeclampsia, and fetal growth restriction. Calcification in the placenta is observed in uncompleted pregnancies, increases with gestational age, and is a hallmark of viral infection. The biomedical significance of placental calcification and/or specific patterns or types of placental calcification remains incompletely understood. Careful experimental design, analysis, and data interpretation are required to study placental calcification. During pregnancy significant maternal hormonal adaptations mobilize minerals enabling unidirectional transport of essential minerals including calcium and phosphorus across the maternal-fetal interface. This process is promoted by active transport by calcium channels and phosphate transporters that move minerals against a concentration gradient at maternal-fetal interface to support embryonic accretion. Indeed, the recent identification of the sodium-dependent phosphate transporter Slc20a2 null mouse as a tractable animal model of placental calcification provides a genetic link and suggests that calcification may be actively regulated and/or programmed throughout gestation. Herein we review studies examining the relationship between placental calcification and clinical outcomes, observed mineral deposits in the placenta, mechanisms of calcium and phosphate homeostasis during pregnancy, and lessons learned about pro- and anti-calcific signaling from both clinical studies and animal models. In closing, we expand on how placental calcification is currently assessed clinically and discuss new frontiers in computer vision and image analysis, which may generate greater confidence in the ability to consider placental calcification in the interpretation of placental disorders.

Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signaling is exquisitely regulated according to specific phases of cardiac development and that RA signaling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signaling by RA receptors (RARs) in early phases of heart development. This article is part of a Special Issue entitled: Nuclear receptors in animal development.