Dcc Regulates Asymmetric Outgrowth of Forebrain Neurons in Zebrafish
- Authors
- Gao, J., Zhang, C., Yang, B., Sun, L., Zhang, C., Westerfield, M., and Peng, G.
- ID
- ZDB-PUB-120522-15
- Date
- 2012
- Source
- PLoS One 7(5): e36516 (Journal)
- Registered Authors
- Peng, Gang, Westerfield, Monte
- Keywords
- none
- MeSH Terms
-
- Tumor Suppressor Proteins/antagonists & inhibitors
- Tumor Suppressor Proteins/genetics
- Tumor Suppressor Proteins/physiology
- Membrane Proteins/antagonists & inhibitors
- Membrane Proteins/genetics
- Membrane Proteins/physiology
- Neurons/cytology
- Prosencephalon/cytology
- Prosencephalon/embryology*
- Recombinant Proteins/genetics
- Recombinant Proteins/metabolism
- Animals, Genetically Modified
- Axons/physiology
- Axons/ultrastructure
- Transcription Factors/genetics
- Transcription Factors/physiology
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- LIM-Homeodomain Proteins/genetics
- LIM-Homeodomain Proteins/physiology
- Luminescent Proteins/genetics
- Luminescent Proteins/metabolism
- Animals
- DNA Primers/genetics
- Base Sequence
- Nerve Growth Factors/antagonists & inhibitors
- Nerve Growth Factors/genetics
- Nerve Growth Factors/physiology
- Chromosomes, Artificial, Bacterial/genetics
- Receptors, Cell Surface/antagonists & inhibitors
- Receptors, Cell Surface/genetics
- Receptors, Cell Surface/physiology*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/physiology*
- Gene Knockdown Techniques
- PubMed
- 22606267 Full text @ PLoS One
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 closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates.