dcc regulates asymmetric outgrowth of forebrain neurons in zebrafishdcc调节不对称斑马鱼前脑神经元的产物.pdf

Dcc Regulates Asymmetric Outgrowth of Forebrain Neurons in Zebrafish 1 1 1 1 1 2 1 Jingxia Gao , Changwen Zhang , Bin Yang , Liu Sun , Cuizhen Zhang , Monte Westerfield , Gang Peng * 1 Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China, 2 Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America Abstract The guidance receptor DCC (deleted in colorectal cancer) ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt) neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor