Neural crest cells (NCCs) are a subset of multipotent, migratory stem cells that populate a large number of tissues during development and are important for craniofacial and cardiac morphogenesis. Although microRNAs (miRNAs) have emerged as important regulators of development and disease, little is known about their role in NCC development. Here, we show that loss of miRNA biogenesis by NCC-specific disruption of murine Dicer results in embryos lacking craniofacial cartilaginous structures, cardiac outflow tract septation and thymic and dorsal root ganglia development.
View Article and Find Full Text PDFThe transcriptional regulation of cardiovascular development requires precise spatiotemporal control of gene expression, and heterozygous mutations of transcription factors have frequently been implicated in human cardiovascular malformations. A novel mechanism involving post-transcriptional regulation by small, noncoding microRNAs (miRNAs) has emerged as a central regulator of many cardiogenic processes. We are beginning to understand the functions that miRNAs play during essential biologic processes, such as cell proliferation, differentiation, apoptosis, stress response, and tumorigenesis.
View Article and Find Full Text PDFMicroRNAs (miRNAs) are regulators of myriad cellular events, but evidence for a single miRNA that can efficiently differentiate multipotent stem cells into a specific lineage or regulate direct reprogramming of cells into an alternative cell fate has been elusive. Here we show that miR-145 and miR-143 are co-transcribed in multipotent murine cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem-cell-derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2-5 (NK2 transcription factor related, locus 5) and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells.
View Article and Find Full Text PDFThe transcriptional regulation of cardiovascular development requires precise spatiotemporal control of gene expression, and heterozygous mutations of transcription factors have frequently been implicated in human cardiovascular malformations. A novel mechanism involving posttranscriptional regulation by small, noncoding microRNAs (miRNAs) has emerged as a central regulator of many cardiogenic processes. We are beginning to understand the functions that miRNAs play during essential biological processes, such as cell proliferation, differentiation, apoptosis, stress response, and tumorigenesis.
View Article and Find Full Text PDFDespite decades of progress in cardiovascular biology, heart disease remains the leading cause of death in the developed world. Recently, cell-based therapy has emerged as a promising avenue for future therapeutics. However, the molecular signals that regulate cardiac progenitor cells are not well-understood.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2008
Organ patterning during embryonic development requires precise temporal and spatial regulation of protein activity. microRNAs (miRNAs), small noncoding RNAs that typically inhibit protein expression, are broadly important for proper development, but their individual functions during organogenesis are largely unknown. We report that miR-138 is expressed in specific domains in the zebrafish heart and is required to establish appropriate chamber-specific gene expression patterns.
View Article and Find Full Text PDFWe demonstrated previously that neonatal proximal tubules have a lower passive paracellular permeability to chloride ions and higher resistance than that of adult proximal tubules. In addition, administration of thyroid hormone to neonates, before the normal maturational increase in serum thyroid hormone levels, prematurely accelerates the developmental increase in chloride permeability to adult levels. To test the hypothesis that there is a maturational change in tight junction proteins and that thyroid hormone mediates these changes, we examined the two known tight junction proteins present in proximal tubules, occludin and claudin 2.
View Article and Find Full Text PDFIschemia-reperfusion injury (I/R injury) is a common cause of acute renal failure. Recovery from I/R injury requires renal tubular regeneration. Hematopoietic stem cells (HSC) have been shown to be capable of differentiating into hepatocytes, cardiac myocytes, gastrointestinal epithelial cells, and vascular endothelial cells during tissue repair.
View Article and Find Full Text PDFPolycystic kidney disease (PKD) is the most common genetic cause of renal failure in humans. Several proteins that are encoded by genes associated with PKD have recently been identified in primary cilia in renal tubular epithelia. These findings have suggested that abnormalities in cilia formation and function may play a role in the pathogenesis of PKD.
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