Heart septation and valve malformations constitute the most common birth defects. These cardiac structures arise from the endocardial cushions through dynamic interactions between cells and the extracellular matrix (cardiac jelly). Targeted deletion of the hyaluronan synthase-2 (Has2) gene in mice results in an absence of cardiac jelly and endocardial cushions, a loss of vascular integrity, and embryonic death at E9.5. Despite the requirements for Has2 and its synthetic product hyaluronan (HA) in the developing cardiovascular system, little is known about the normal expression pattern of Has2 or the factors regulating Has2 gene transcription during development. Bmp signaling is an important regulator of cardiac myogenesis, and is also important for endocardial cushion formation. The current study defines the embryonic expression pattern of Has2 and explores the regulation of Has2 gene expression by Bmp signaling. In situ hybridization studies demonstrate dynamic Has2 expression patterns during myocardial cell development and cardiac tube formation, formation of the cardiac endocardial cushions, and cushion invasion by valve primordial cells. Despite overlapping regional expression of Bmp2 in the late gastrula anterior lateral endoderm and Has2 in the adjacent cardiogenic mesoderm, application of noggin-expressing CHO cells beneath the endoderm failed to perturb normal Has2 expression. Thus, in contrast to many genes expressed in the heart forming region, regulation of Has2 in the cardiogenic mesoderm is independent of Bmp signaling. © 2005 Elsevier B.V. All rights reserved.
PMID: 16983084;PMCID: PMC1599972;Abstract:
MicroRNAs (miRNAs) attenuate gene expression by means of translational inhibition and mRNA degradation. They are abundant, highly conserved, and predicted to regulate a large number of transcripts. Several hundred miRNA classes are known, and many are associated with cell proliferation and differentiation. Many exhibit tissue-specific expression, which aids in evaluating their functions, and it has been assumed that their high level of sequence conservation implies a high level of expression conservation. A limited amount of data supports this, although discrepancies do exist. By comparing the expression of ≈100 miRNAs in medaka and chicken with existing data for zebrafish and mouse, we conclude that the timing and location of miRNA expression is not strictly conserved. In some instances, differences in expression are associated with changes in miRNA copy number, genomic context, or both between species. Variation in miRNA expression is more pronounced the greater the differences in physiology, and it is enticing to speculate that changes in miRNA expression may play a role in shaping the physiological differences produced during animal development. © 2006 by The National Academy of Sciences of the USA.
There are no known differences between the mechanisms that generate diverse differentiation programs in a mosaic embryo such as Caenorhabdites elegans or in a regulative embryo such as a chick. Transit through an invariant sequence of compartments in a lineage is obligatory for a given precursor cell 1) to inherit its differentiation program from its mother, and 2) to transmit to its daughters, by way of a predetermined binary decision, a new differentiation program. The inheritability of a differentiation program must be encoded in a structural molecule. We postulate that during an S period of a quantal cell cycle, chromosomal structures are so altered that a network of genes that could not be transcribed in the mother becomes available for transcription in the daughters. We do not view as a likely possibility the traditional notion that cell-cell or cell-matrix interactions instruct or commit blank, naive cells to transform into cells with unique differentiation programs. From this perspective, we have initiated experiments to determine the minimal rounds of DNA synthesis, following fertilization, that are required to generate founder cells for several major lineages in the chick. Somewhere between the 15th and 18th generations after fertilization erythrogenic hematocytoblasts that are cytokeratin-positive and vimentin- and hemoglobin-negative undergo a quantal cell cycle. Their daughters are cytokeratin-negative and vimentin- and hemoglobin-positive. DNA synthesis, but not cytokinesis, is an obligatory requirement for this switch in differentiation programs. Essentially similar findings are presented for cells in the cardiogenic, neurogenic, melanogenic, and endothelial lineages. There is no evidence that cell-cell or cell-matrix interactions are required for this diversification. Such interactions, however, may be required for the large number of proliferative cell cycles within particular compartments of particular lineages that are characteristic of all growing or expanding systems. With respect to classical "CFU cells" it is of interest that definitive white blood cells have not yet been identified in these cultures. Lastly, the high ratio of primitive red blood cells to non-red blood cells in the first 40 hours of culture is consistent with the notion that the majority of all cells present in the blastodisc at these early stages are in fact already committed to a unipotent erythrogenic lineage [5, 18, 23, 44, 45]. The issue of changing ratios of cells within compartments of a lineage, as well as of cells in different lineages, is much neglected in consideration of (a) normal embryogenesis, (b) cell-renewal in mature organisms and, particularly,