J. Dev. Biol.2014, 2(2), 101-116; doi:10.3390/jdb2020101 - published online 11 April 2014 Show/Hide Abstract
Abstract: The epicardium is the mesothelial outer layer of the vertebrate heart. It plays an important role during cardiac development by, among other functions, nourishing the underlying myocardium, contributing to cardiac fibroblasts and giving rise to the coronary vasculature. The epicardium also exerts key functions during injury responses in the adult and contributes to cardiac repair. In this article, we review current knowledge on the cellular and molecular mechanisms underlying epicardium formation in the zebrafish, a teleost fish, which is rapidly gaining status as an animal model in cardiovascular research, and compare it with the mechanisms described in other vertebrate models. We moreover describe the expression patterns of a subset of available zebrafish Wilms’ tumor 1 transgenic reporter lines and discuss their specificity, applicability and limitations in the study of epicardium formation.
J. Dev. Biol.2014, 2(2), 84-100; doi:10.3390/jdb2020084 - published online 10 April 2014 Show/Hide Abstract
Abstract: In the last decade, cell replacement therapy has emerged as a potential approach to treat patients suffering from myocardial infarction (MI). The transplantation or local stimulation of progenitor cells with the ability to form new cardiac tissue provides a novel strategy to overcome the massive loss of myocardium after MI. In this regard the epicardium, the outer layer of the heart, is a tractable local progenitor cell population for therapeutic pursuit. The epicardium has a crucial role in formation of the embryonic heart. After activation and migration into the developing myocardium, epicardial cells differentiate into several cardiac cells types. Additionally, the epicardium provides instructive signals for the growth of the myocardium and coronary angiogenesis. In the adult heart, the epicardium is quiescent, but recent evidence suggests that it becomes reactivated upon damage and recapitulates at least part of its embryonic functions. In this review we provide an update on the current knowledge regarding the contribution of epicardial cells to the adult mammalian heart during the injury response.
J. Dev. Biol.2014, 2(2), 72-83; doi:10.3390/jdb2020072 - published online 8 April 2014 Show/Hide Abstract
Abstract: One of the more intriguing subjects in neuroscience is how a precursor or stem cell is induced to differentiate into a neuron. Neurogenesis begins early in brain development and suddenly becomes a very intense process, which is related with the influence of Retinoic Acid. Here, using a biological test (F9-1.8 cells) in chick embryos, we show that “in vivo” embryonic cerebrospinal fluid regulates mesencephalic-rombencephalic Isthmic Retinoic Acid synthesis and this effect has a direct influence on mesencephalic neuroepithelial precursors, inducing a significant increase in neurogenesis. This effect is mediated by the Retinol Binding Protein present in the embryonic cerebrospinal fluid. The knowledge of embryonic neurogenetic stimulus could be useful in the control of adult brain neurogenesis.
J. Dev. Biol.2014, 2(1), 50-71; doi:10.3390/jdb2010050 - published online 21 March 2014 Show/Hide Abstract
Abstract: Retinoic acid (RA), a derivative of vitamin A, is involved in signal transduction during vertebrate organogenesis. Retinoids through binding to nuclear receptors called RA receptors (RARs) and retinoid X receptors (RXRs) regulate various processes during cardiogenesis. Deregulated retinoid signaling thus has later consequences leading to cardiac malformations. In this review, we will summarize and discuss our current knowledge on the role of RA signaling during heart development, especially during patterning of the heart fields. We have also integrated recent experiments essential for our understanding of the role of RA signaling during epicardial development and myocardial growth.
J. Dev. Biol.2014, 2(1), 34-49; doi:10.3390/jdb2010034 - published online 21 March 2014 Show/Hide Abstract
Abstract: Vitamin A has been shown to be essential for a multitude of biological processes vital for mammalian development and homeostasis. Its active metabolite, retinoic acid (RA), is important for establishing and maintaining proper germ cell development. During spermatogenesis, the germ cells orient themselves in very distinct patterns, which have been organized into stages. There is evidence to show that, in the mouse, RA is needed for many steps during germ cell development. Interestingly, RA has been implicated as playing a role within the same two Stages: VII and VIII, where meiosis is initiated and spermiation occurs. The goal of this review is to outline this evidence, exploring the relevant players in retinoid metabolism, storage, transport, and signaling. Finally, this review will provide a potential model for how RA activity is organized across the murine stages of the spermatogenic cycle.
J. Dev. Biol.2014, 2(1), 18-33; doi:10.3390/jdb2010018 - published online 17 March 2014 Show/Hide Abstract
Abstract: Embryonic and adult hematopoiesis are both finely regulated by a number of signaling mechanisms. In the mammalian embryo, short-term and long-term hematopoietic stem cells (HSC) arise from a subset of endothelial cells which constitute the hemogenic endothelium. These HSC expand and give rise to all the lineages of blood cells in the fetal liver, first, and in the bone marrow from the end of the gestation and throughout the adult life. The retinoic acid (RA) signaling system, acting through the family of nuclear retinoic acid receptors (RARs and RXRs), is involved in multiple steps of the hematopoietic development, and also in the regulation of the differentiation of some myeloid lineages in adults. In humans, the importance of this RA-mediated control is dramatically illustrated by the pathogeny of acute promyelocytic leukemia, a disease produced by a chromosomal rearrangement fusing the RARa gene with other genes. The aberrant fusion protein is able to bind to RARα target gene promoters to actively suppress gene transcription. Lack of function of RARα leads to a failure in the differentiation of promyelocytic progenitors. In this review we have collected the available information about all the phases of the hematopoietic process in which RA signaling is involved, being essential for steps such as the emergence of HSC from the hemogenic endothelium, or modulating processes such as the adult granulopoiesis. A better knowledge of the RA-mediated signaling mechanisms can contribute to the knowledge of the origin of many pathologies of the hematopoietic system and can provide new clinical avenues for their treatment.