During cell migration, the actin cytoskeleton regulator, RhoA, must be alternately inhibited (to allow the leading membrane edge to protrude) and reactivated (to pull up the trailing end of the cell from behind). Inhibition occurs when a receptor called 5β1 integrin, which binds to the extracellular matrix protein, fibronectin, triggers phosphorylation of a RhoA inhibitor called p190RhoGAP-A (p190-A). Another fibronectin receptor, syndecan-4, colocalizes with integrin during RhoA inhibition, but whether this second receptor contributes to inhibition was unknown.
"The migration is initiated by the change of endothelial precursors to their migratory phenotype. The endothelial precursor cells are then guided to the position where the primary vascular plexus is formed. Migration is stopped by the reversion of the cells to their nonmigratory phenotype. A combination of regulatory mechanisms and factors controls this process. These include gradients of soluble factors, extracellular matrix–cell interaction and cell–cell interaction. "
Johns Hopkins researchers have found a way to directly observe cell migration -- in real time and in living tissue. In a report in the June 5 issue of Developmental Cell, the scientists say their advance could lead to strategies for controlling both normal growth and the spread of cancer, processes that depend on the programmed, organized movement of cells across space.
"The physical properties of the cellular environment are involved in regulating the formation and maintenance of tissues. In particular, substrate rigidity appears to be a key factor dictating cell response on culture surfaces. Here we study the behavior of epithelial cells cultured on microfabricated substrates engineered to exhibit an anisotropic stiffness. The substrate consists of a dense array of micropillars of oval cross-section, so that one direction is made stiffer than the other
Plasminogen activator inhibitor-1 (PAI-1) is a primary regulator of urokinase-type plasminogen activator (uPA). It inhibits uPA by forming a covalent complex, thus blocking uPA’s interaction with substrates. The half-life of active PAI-1 is < 1 h and it is easily transformed to a more stable inactive latent form. By binding with vitronectin, PAI-1 can be stabilized and remained its activity. PAI-1 expression is regulated by many intrinsic factors (e.g. cytokines, growth factors, hormones, and lipids) and extrinsic factors (e.g. physical injury and DNA-damaging agents)
"Wnt signaling cascades activate morphogenetic programs that range from cell migration and proliferation to cell fate determination and stem cell renewal. These pathways enable cells to translate environmental cues into the complex cellular programs that are needed to organize tissues and build organs."
“Lymphocyte migration is activated in response to inflammation and largely depends on the modulation of actin dynamics, and remodelling of the cytoskeleton, following cytokine stimulation. A novel pathway modulating inflammatory-cell migration in vivo that involves the unlikeliest of partners, the inflammatory caspase-11 and Aip1 (an activator of cofilin-mediated actin depolymerization), has been identified.”
Embryonic stem cells rely on Polycomb group proteins to reversibly repress genes required for differentiation. We report that stem cell Polycomb group targets are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation than non-targets, supporting a stem cell origin of cancer in which reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and thereby predisposing to subsequent malignant transformation.
Its guidelines also diverge from those of the NAS regarding the creation of chimeras by injecting animals with human embryonic stem cells. Both the NAS and the ISSCR outlaw the mating of adult chimeras with each other, as this could accidentally create a human embryo inside an animal. The NAS guidelines also oppose the mating of chimeras with non-chimeras, and while the ISSCR calls for a strict local review of these kinds of experiments it does not rule them out
[Full Text]Genetic studies of behavior in the nematode Caenorhabditis elegans have provided an effective approach to investigate the molecular and cellular basis of nervous system function and development. Among the best studied behaviors is egg-laying, the process by which hermaphrodites deposit developing embryos into the environment. Egg-laying involves a simple motor program involving a small network of motorneurons and specialized smooth muscle cells, which is regulated by a variety of sensory stimuli