Although it appears that wild-type human FUS maintains an intrinsic ability to accumulate in SGs and that the increased extent of SG accumulation for mutant FUS may be due to increased absolute protein levels in the cytosol not to the mutations themselves. Some studies have shown that overexpression of FUS-WT can have a toxic effect, leading to ALS-like phenotypes such as toxic cytoplasmic inclusions in yeast and motor neuron degeneration and loss of neurons in the brains of rats. We did not so far observe any obvious toxicity of wild-type or mutant FUS-GFP at least at the larval stage in zebrafish, although transgenic zebrafish models expressing ALS mutant TDP-43 or SOD1, exhibit aberrant axonal branching, shortening of axons and an aberrant motor phenotype at later stages of development. SMBA 1 Recent work has demonstrated impairment of neuromuscular synaptic transmission in the larval stage of zebrafish transiently expressing mutant human FUS. Further investigation of the transgenic zebrafish human FUS lines will enable these questions to be further addressed and the effects of cell autonomous versus non-autonomous effects of mislocalized and mutant FUS on the development, function and survival of motor neuron. The power of the approach described in this study is to complement investigations in whole fish with deduction of the cellular mechanisms at work in ALS in vitro using cell cultures derived from relatively easily generated transgenic zebrafish models. Impaired bone regeneration following injury or under pathological conditions causes severe pain to the patients and considerable financial burden to the society. These conditions include delayed fracture union or non-union, osteoporotic fracture healing, impaired bone repair associated with diabetes, and large bone defects caused by trauma or surgical treatments. Hallmarks of impaired bone repair in patients and animal models include the deficiency in vascular supply and RWJ 50271 cartilaginous callus formation at the site of injury, suggesting that impaired angiogenic and chondrogenic responses are major contributors to the pathology. Bone regeneration is a complex process in which the recovery of skeletal tissue integrity relies upon close temporal and spatial coordination of molecular and cellular events involving resident bone cells, inflammatory cells, marrow stromal elements, and associated vascular structures to achieve structural reconstitution and bone remodeling.