Learn More
MicroRNAs (miRNAs) are genomically encoded small RNAs that hybridize with messenger RNAs, resulting in degradation or translational inhibition of targeted transcripts. The potential for miRNAs to regulate cell-lineage determination or differentiation from pluripotent progenitor or stem cells is unknown. Here, we show that microRNA1 (miR-1) is an ancient(More)
Guiding multipotent cells into distinct lineages and controlling their expansion remain fundamental challenges in developmental and stem cell biology. Members of the Wnt pathway control many pivotal embryonic events, often promoting self-renewal or expansion of progenitor cells. In contrast, canonical Wnt ligands are thought to negatively regulate(More)
Cellular decisions of self-renewal or differentiation arise from integration and reciprocal titration of numerous regulatory networks. Notch and Wnt/β-catenin signalling often intersect in stem and progenitor cells and regulate each other transcriptionally. The biological outcome of signalling through each pathway often depends on the context and timing as(More)
Notch is an ancient transmembrane receptor with crucial roles in cell-fate choices. Although the 'canonical' Notch pathway and its core members are well established - involving ligand-induced cleavage of Notch for transcriptional regulation - it has been unclear whether Notch can also function independently of ligand and transcription ('non-canonically')(More)
Despite 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. Wnt/beta-catenin signaling is essential for(More)
Regulation of multipotent cardiac progenitor cell (CPC) expansion and subsequent differentiation into cardiomyocytes, smooth muscle or endothelial cells is a fundamental aspect of basic cardiovascular biology and cardiac regenerative medicine. However, the mechanisms governing these decisions remain unclear. Here, we show that Wnt/beta-catenin signalling,(More)
We analyze the structure of stochastic dynamics near either a stable or unstable fixed point, where the force can be approximated by linearization. We find that a cost function that determines a Boltzmann-like stationary distribution can always be defined near it. Such a stationary distribution does not need to satisfy the usual detailed balance condition(More)
The sensory organs of the Drosophila adult leg provide a simple model system with which to investigate pattern-forming mechanisms. In the leg, a group of small mechanosensory bristles is organized into a series of longitudinal rows, a pattern that depends on periodic expression of the hairy gene (h) and the proneural genes achaete (ac) and scute (sc).(More)
Decades of progress in developmental cardiology has advanced our understanding of the early aspects of heart development, including cardiomyocyte (CM) differentiation. However, control of the CM maturation that is subsequently required to generate adult myocytes remains elusive. Here, we analyzed over 200 microarray datasets from early embryonic to adult(More)
Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. However, cGMP stimulation(More)