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Heart Field (heart + field)
Selected AbstractsSecond lineage of heart forming region provides new understanding of conotruncal heart defectsCONGENITAL ANOMALIES, Issue 1 2010Yuji Nakajima ABSTRACT Abnormal heart development causes various congenital heart defects. Recent cardiovascular biology studies have elucidated the morphological mechanisms involved in normal and abnormal heart development. The primitive heart tube originates from the lateral-most part of the heart forming mesoderm and mainly gives rise to the left ventricle. Then, during the cardiac looping, the outflow tract is elongated by the addition of cardiogenic cells from the both pharyngeal and splanchnic mesoderm (corresponding to anterior and secondary heart field, respectively), which originate from the mediocaudal region of the heart forming mesoderm and are later located anteriorly (rostrally) to the dorsal region of the heart tube. Therefore, the heart progenitors that contribute to the outflow tract region are distinct from those that form the left ventricle. The knowledge that there are two different lineages of heart progenitors in the four-chambered heart provides new understanding of the morphological and molecular etiology of conotruncal heart defects. [source] Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesisDEVELOPMENTAL DYNAMICS, Issue 7 2010Jeremy L. Barth Abstract Nkx2.5, a transcription factor implicated in human congenital heart disease, is required for regulation of second heart field (SHF) progenitors contributing to outflow tract (OFT). Here, we define a set of genes (Lrrn1, Elovl2, Safb, Slc39a6, Khdrbs1, Hoxb4, Fez1, Ccdc117, Jarid2, Nrcam, and Enpp3) expressed in SHF containing pharyngeal arch tissue whose regulation is dependent on Nkx2.5. Further investigation shows that Jarid2, which has been implicated in OFT morphogenesis, is a direct target of Nkx2.5 regulation. Jarid2 expression was up-regulated in SHF mesoderm of Nkx2.5-deficient embryos. Chromatin immunoprecipitation analysis showed Nkx2.5 interaction with consensus binding sites in the Jarid2 promoter in pharyngeal arch cells. Finally, Jarid2 promoter activity and mRNA expression levels were down-regulated by Nkx2.5 overexpression. Given the role of Jarid2 as a regulator of early cardiac proliferation, these findings highlight Jarid2 as one of several potential mediators of the critical role played by Nkx2.5 during OFT morphogenesis. Developmental Dynamics 239:2024,2033, 2010. © 2010 Wiley-Liss, Inc. [source] The lim domain only protein 7 is important in zebrafish heart developmentDEVELOPMENTAL DYNAMICS, Issue 12 2008Elisabeth B. Ott Abstract The LIM domain only protein 7 (LMO7), a member of the PDZ and LIM domain-containing protein family is a candidate gene with possible roles in embryonic development and breast cancer progression. LMO7 has been linked to actin cytoskeleton organization through nectin/afadin and to cell,cell adhesion by means of E-cadherin/catenin. In addition, LMO7 has been shown to regulate transcription of the nuclear membrane protein Emerin and other muscle relevant genes. In this study, we used in situ hybridization to investigate LMO7 expression during embryonic development in three widely used vertebrate model species: the zebrafish, the chicken and the mouse. Our temporal and spatial gene expression analysis revealed both common and distinct patterns between these species. In mouse and chicken embryos we found expression in the outflow tract, the inflow tract, the pro-epicardial organ and the second heart field, structures highly important in the developing heart. Furthermore, gene knockdown experiments in zebrafish embryos resulted in severe defects in heart development with effects on the conduction system and on heart localization. In summary, we present here the first developmental study of LMO7. We reveal the temporal and spatial expression patterns of this important gene during mouse, chicken and fish development and our findings suggest essential functions for LMO7 during vertebrate heart development. Developmental Dynamics 237:3940,3952, 2008. © 2008 Wiley-Liss, Inc. [source] Origin and fate of cardiac mesenchymeDEVELOPMENTAL DYNAMICS, Issue 10 2008Brian S. Snarr Abstract The development of the embryonic heart is dependent upon the generation and incorporation of different mesenchymal subpopulations that derive from intra- and extra-cardiac sources, including the endocardium, epicardium, neural crest, and second heart field. Each of these populations plays a crucial role in cardiovascular development, in particular in the formation of the valvuloseptal apparatus. Notwithstanding shared mechanisms by which these cells are generated, their fate and function differ profoundly by their originating source. While most of our early insights into the origin and fate of the cardiac mesenchyme has come from experimental studies in avian model systems, recent advances in transgenic mouse technology has enhanced our ability to study these cell populations in the mammalian heart. In this article, we will review the current understanding of the role of cardiac mesenchyme in cardiac morphogenesis and discuss several new paradigms based on recent studies in the mouse. Developmental Dynamics 237:2804,2819, 2008. © 2008 Wiley-Liss, Inc. [source] Effects of antisense misexpression of CFC on downstream flectin protein expression during heart loopingDEVELOPMENTAL DYNAMICS, Issue 2 2003Kersti K. Linask Abstract Dextral looping of the heart is regulated on multiple levels. In humans, mutations of the genes CFC and Pitx2/RIEG result in laterality-associated cardiac anomalies. In animal models, a common read-out after the misexpression of laterality genes is heart looping direction. Missing in these studies is how laterality genes impact on downstream morphogenetic processes to coordinate heart looping. Previously, we showed that Pitx2 indirectly regulates flectin protein by regulating the timing of flectin expression in one heart field versus the other (Linask et al. [2002] Dev. Biol. 246:407,417). To address this question further we used a reported loss-of-function approach to interfere with chick CFC expression (Schlange et al. [2001] Dev. Biol. 234:376,389) and assaying for flectin expression during looping. Antisense CFC treatment results in abnormal heart looping or no looping. Our results show that regardless of the sidedness of downstream Pitx2 expression, it is the sidedness of predominant flectin protein expression in the extracellular matrix of the dorsal mesocardial folds and splanchnic mesoderm apposed to the foregut wall that is associated directly with looping direction. Thus, Pitx2 can be experimentally uncoupled from heart looping. The flectin asymmetry continues to be maintained in the secondary heart field during looping. Developmental Dynamics 228:217,230, 2003. © 2003 Wiley-Liss, Inc. [source] Cardiovascular abnormalities in Folr1 knockout mice and folate rescue,BIRTH DEFECTS RESEARCH, Issue 4 2007Huiping Zhu Abstract BACKGROUND: Periconceptional folic acid supplementation is widely believed to aid in the prevention of neural tube defects (NTDs), orofacial clefts, and congenital heart defects. Folate-binding proteins or receptors serve to bind folic acid and 5-methyltetrahydrofolate, representing one of the two major mechanisms of cellular folate uptake. METHODS: We herein describe abnormal cardiovascular development in mouse fetuses lacking a functional folate-binding protein gene (Folr1). We also performed a dose-response study with folinic acid and determined the impact of maternal folate supplementation on Folr1 nullizygous cardiac development. RESULTS: Partially rescued preterm Folr1,/, (formerly referred to as Folbp1) fetuses were found to have outflow tract defects, aortic arch artery abnormalities, and isolated dextracardia. Maternal supplementation with folinic acid rescued the embryonic lethality and the observed cardiovascular phenotypes in a dose-dependant manner. Maternal genotype exhibited significant impact on the rescue efficiency, suggesting an important role of in utero folate status in embryonic development. Abnormal heart looping was observed during early development of Folr1,/, embryos partially rescued by maternal folinic acid supplementation. Migration pattern of cardiac neural crest cells, genetic signals in pharyngeal arches, and the secondary heart field were also found to be affected in the mutant embryos. CONCLUSIONS: Our observations suggest that the beneficial effect of folic acid for congenital heart defects might be mediated via its impact on neural crest cells and by gene regulation of signaling pathways involved in the development of the pharyngeal arches and the secondary heart field. Birth Defects Research (Part A) 2007. © 2007 Wiley-Liss, Inc. [source] Developmental analysis of activin-like kinase receptor-4 (ALK4) expression in Xenopus laevisDEVELOPMENTAL DYNAMICS, Issue 2 2005Yumei Chen Abstract The type I transforming growth factor-beta (TGF,) receptor, activin-like kinase-4 (ALK4), is an important regulator of vertebrate development, with roles in mesoderm induction, primitive streak formation, gastrulation, dorsoanterior patterning, and left,right axis determination. To complement previous ALK4 functional studies, we have analyzed ALK4 expression in embryos of the frog, Xenopus laevis. Results obtained with reverse transcriptase-polymerase chain reaction indicate that ALK4 is present in both the animal and vegetal poles of blastula stage embryos and that expression levels are relatively constant amongst embryos examined at blastula, gastrula, neurula, and early tail bud stages. However, the tissue distribution of ALK4 mRNA, as assessed by whole-mount in situ hybridization, was found to change over this range of developmental stages. In the blastula stage embryo, ALK4 is detected in cells of the animal pole and the marginal zone. During gastrulation, ALK4 is detected in the outer ectoderm, involuting mesoderm, blastocoele roof, dorsal lip, and to a lesser extent, in the endoderm. At the onset of neurulation, ALK4 expression is prominent in the dorsoanterior region of the developing head, the paraxial mesoderm, and midline structures, including the prechordal plate and neural folds. Expression in older neurula stage embryos resolves to the developing brain, somites, notochord, and neural crest; thereafter, additional sites of ALK4 expression in tail bud stage embryos include the spinal cord, otic placode, developing eye, lateral plate mesoderm, branchial arches, and the bilateral heart fields. Together, these results not only reflect the multiple developmental roles that have been proposed for this TGF, receptor but also define spatiotemporal windows in which ALK4 may function to modulate fundamental embryological events. Developmental Dynamics 232:393,398, 2005. © 2004 Wiley-Liss, Inc. [source] | ||||||||||