Anti-Mmp14a+b polyclonal antibody

Synaptic vesicles are indispensable for neuronal communication in mature circuits. Synaptic vesicle biogenesis must be concurrent with axon navigation for synaptogenesis, but whether synaptic vesicles are functionally employed in circuit formation before synaptogenesis is poorly understood. Here, we use time-lapse imaging and transgenesis in zebrafish to visualize the role of synaptic-like vesicles in navigation of dorsal root ganglia pioneer axons. We identify that synaptic-like vesicles accumulate in the central growth cone as the pioneer axon breaches the spinal boundary at the dorsal root entry zone. Inhibition of vesicle release with cell-specific tetanus toxin expression results in pioneer axon pathfinding defects and altered spinal entry. We further show that the matrix metalloproteinase (MMP) mmp14a is required in pioneer axons to navigate across the boundary of the spinal cord and, with super-resolution microscopy, is positioned with synaptic vesicles at the boundary. Manipulations of concurrent actin reorganization reveal that actin remodeling drives vesicle release and subsequent MMP activity. Together, these data point to an indispensable role for synaptic-like vesicles at specific points in axon navigation as regulators of growth cone microenvironment.

Fish have been used as laboratory models to study hepatic development and carcinogenesis but not for pathogenesis of hepatic fibrosis. In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka (Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. Exposed livers exhibited mild hepatocellular degenerative changes 2 weeks' postexposure. Within 6 weeks, hepatic fibrosis/cirrhosis was evident with development of neoplasia by 10 weeks. Stellate cell activation and development of fibrosis was associated with upregulation of transforming growth factor beta 1 (tgfb1), tgfb receptor 2, mothers against decapentaplegic homolog 3 (smad3a), smad3b, beta-catenin (ctnnb1), myc, matrix metalloproteinase (mmp2), mmp14a, mmp14b, tissue inhibitors of metalloproteinase (timp) 2a, timp2b, timp3, collagen type I alpha 1a (col1a1a), and col1a1b and a less pronounced increase in mmp13 and col4a1 expression. Tgfb receptor I expression was unchanged. Immunohistochemistry suggested that biliary epithelial cells and stellate cells were the main producers of TGF-1. This study identified a group of candidate genes likely to be involved in the development of hepatic fibrosis and demonstrated that the TGF- pathway likely plays a major role in the pathogenesis. These results support the medaka as a viable fish model of hepatic fibrosis.