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Expression of epidermal growth factor receptor in chick embryo myocardiocytes: relation with desmin expression during cardiac development.

The epidermal growth factor receptor is related with processes of cell replication and differentiation. We used the intermediate filament protein desmin as a marker to study the relation between muscle cell differentiation and modifications in the expression of this receptor during heart development in the chick embryo. Epidermal growth factor receptor was expressed as early as Hamburger and Hamilton's stage 17, when myocardiocytes are still poorly differentiated and desmin-negative. Expression became steadily weaker as the heart matured, and decreased after Hamburger and Hamilton's stage 25, a key stage in heart maturation characterized by a sharp increase in desmin expression. Our findings suggest that in the chick embryo, the expression of epidermal growth factor receptor becomes steadily weaker as myocardiocyte differentiation progresses.

Animals↗

Toxic effects of maternal methadone administration on cardiac development in the neonatal rat: potential participation of altered polyamine levels in growth impairment.

The pattern of development of polyamine levels in hearts of preweanling rats whose mothers received methadone indicated initial deficits in both spermidine and spermine followed by rebound elevations, a pattern consistent with delayed cellular development. Since polyamines are thought to play important roles in nucleic acid and protein synthesis during cellular maturation, these alterations may participate in the retardation of tissue growth seen in the perinatal opiate syndrome.

Aging↗

Post-transcriptional regulation of the cystic fibrosis gene in cardiac development and hypertrophy.

Eukaryotic gene expression, reflected in the amount of steady-state mRNA, is regulated at the post-transcriptional level. The 5'-untranslated regions (5'-UTRs) of some transcripts contain cis-acting elements, including upstream open reading frames (uORFs), that have been identified as being fundamental in modulating translation efficiency and mRNA stability. Previously, we demonstrated that uORFs present in the 5'-UTR of cystic fibrosis transmembrane conductance regular (CFTR) transcripts expressed in the heart were able to modulate translation efficiency of the main CFTR ORF. Here, we show that the same 5'-UTR elements are associated with the differential stability of the 5'-UTR compared to the main coding region of CFTR transcripts. Furthermore, these post-transcriptional mechanisms are important factors governing regulated CFTR expression in the heart, in response to developmental and pathophysiological stimuli.

5' Untranslated Regions↗

Essential role of Hand2 in interventricular septum formation and trabeculation during cardiac development.

Interventricular septum (IVS) formation is one of the key events in the development of a four-chambered heart. We previously showed that the basic helix-loop-helix transcription factor Hand1 plays an important role in the formation of the IVS. Here, we found that the other Hand gene, Hand2, regulated expansion, trabeculation, and IVS formation in the embryonic heart. In transgenic embryos expressing Hand2 in the whole ventricles, the boundary region between the left and right ventricles expanded outwards, resulting in complete absence of the IVS. Moreover, trabecular formation was observed even in a region where the IVS was expected to form. In some transgenic embryos with heterogeneous expression of the transgene, a muscular septum did not form in a region where Hand2 was expressed, but an incomplete septum was identifiable in a region where Hand2 was not expressed, suggesting that septum formation was strictly regulated by the expression domain of Hand2. Furthermore, expression of trabecular markers including ANF, BNP, and connexin40 was significantly up-regulated in the ventricles of Hand2 transgenic embryos as well as in H9c2 cells over-expressing Hand2. These results suggested that the absence of Hand2 expression in the interventricular boundary region inhibits expansion and trabeculation in this area, contributing to the proper formation of the IVS.

Animals↗

Cardiac development: new concepts.

Understanding normal development is a prerequisite to unraveling the mechanisms that underlie congenital heart disease, a critical step if one is to design rational new therapies. Over the past 20 years, human molecular genetics and developmental biology have provided a group of powerful tools to uncover a number of now well-defined pathways. There is now a confluence of new technologies and experimental systems that may allow for a more profound understanding in the near future.

GATA4 Transcription Factor↗

Ciona intestinalis as a model for cardiac development.

The primitive chordate Ciona intestinalis has emerged as a significant model system for the study of heart development. The Ciona embryo employs a conserved heart gene network in the context of extremely low cell numbers and reduced genetic redundancy. Here, I review recent studies on the molecular genetics of Ciona cardiogenesis as well as classic work on heart anatomy and physiology. I also discuss the potential of employing Ciona to decipher a comprehensive chordate gene network and to determine how this network controls heart morphogenesis.

Animals↗

Cell biology of cardiac development.

Building a vertebrate heart is a complex task and involves several tissues, including the myocardium, endocardium, neural crest, and epicardium. Interactions between these tissues result in the changes in function and morphology (and also in the extracellular matrix, which serves as a substrate for morphological change) that are requisite for development of the heart. Some of the signaling pathways that mediate these changes have now been identified and several investigators are now filling in the missing pieces in these pathways in hopes of ultimately understanding the molecular mechanisms that govern healthy heart development. In addition, transcription factors that regulate various aspects of heart development have been identified. Transcription factors of the GATA and Nkx2 families are of particular importance for early specification of the heart field and for regulating expression of genes that encode proteins of the contractile apparatus. This chapter highlights some of the most significant discoveries made in the rapidly expanding field of heart development.

Animals↗

Cardiac development and perinatal care of infants with neural crest-associated conotruncal defects.

The neural crest constitutes a developmental field which is a morphogenetically reactive unit of the embryo. Disruption of this developmental field causes a constellation of anomalies to occur. Clustering of phenotypic abnormalities has allowed clinicians to recognize neural crest-associated syndromes with developmental abnormalities of the cardiovascular system, head, and neck. Basic research is beginning to unravel how these phenotypic characteristics are related to specific gene defects expressed during development. Currently, we do not know a one-to-one relationship between phenotypes and genotypes. These neonates with neural crest-associated conotruncal defects are born with recognizable complex cyanotic heart defects that are ductal-dependent. It may be difficult to judge if they have DiGeorge or velocardiofacial syndromes; thus, genetic counseling is of importance. Besides their life-threatening cardiovascular defects, these neonates frequently have either transient or persistent hypocalcemia or severe immunodeficiencies that require critical care management. This review will focus on the basic research underpinnings and currently recommended clinical care of infants with neural crest-associated conotruncal defects.

Animals↗

Wetness of the nest environment influences cardiac development in pre- and post-natal snapping turtles (Chelydra serpentina).

We dissected hearts from near-term embryos and hatchlings of common snapping turtles (Chelydridae: Chelydra serpentina) whose eggs had incubated on wet or dry substrates, and then dried and individually weighed the heart and yolk-free carcass from each animal. Hearts and carcasses of prenatal and neonatal animals grew at different rates, and the patterns of growth by both heart and carcass differed between wet and dry environments. Hearts grew faster, both in actual mass and in mass adjusted for variation in body size, in embryos and hatchlings whose eggs were incubated on dry substrates than in animals whose eggs were held on wet media. This finding is consistent with a hypothesis that embryos incubating in dry settings experience hypovolemia secondary to dehydration and that enlargement of the heart compensates, in part, for the associated increase in viscosity of the blood. Embryonic turtles seemingly exhibit the same plasticity and response that would be expected from other vertebrate ectotherms subjected to the physiological challenges associated with desiccation and an associated reduction in blood volume.

Animals↗

Influence of thyroid hormone on the tissue-specific expression of cytochrome c oxidase isoforms during cardiac development.

In mammals, cytochrome c oxidase (COX) is composed of 13 different protein subunits. In the rat, two nuclear-encoded subunits, COX VIa and VIII, exist as tissue-specific isoforms: heart and liver. Using Northern-blot analysis, the levels of transcripts for the heart and liver isoforms of VIa and VIII were examined in developing rat hearts. The liver isoform was found to be the predominant form of subunit VIa and the exclusive form of VIII in the 18-day fetal hearts. The mRNA levels of the heart isoform of both subunits increased dramatically to reach adult levels by 14 days. Although the levels of the VIa- and VIII-liver isoform mRNAs remained stable throughout early development, their levels decreased by 40 and 36% respectively between the 18-day fetal stage and 18-day neonatal stage. Therefore the up-regulation of the heart isoforms and down-regulation of the liver isoforms appear to be regulated in a co-ordinated manner during development. To determine if thyroid hormone influences the expression of these developmentally regulated isoforms, the RNA was also extracted from the hearts of 2-week-old hypothyroid rats. The results showed that the levels of VIII-heart and VIa-liver COX mRNAs were approx. 40% lower in the hypothyroid hearts, while VIII-liver and VIa-heart COX isoform expression remained unchanged. These data demonstrate that the isoforms of COX subunits VIa and VIII are not co-ordinately regulated by changes in thyroid hormone levels. Therefore we conclude that, although thyroid hormone influences the expression of isoforms, it appears to do so via a different mechanism from that which regulates the developmental transition.

Animals↗