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
-
- Animals
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/physiology*
- Axons/physiology
- Axons/ultrastructure
- Base Sequence
- Membrane Proteins/antagonists & inhibitors
- Membrane Proteins/genetics
- Membrane Proteins/physiology
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- Gene Knockdown Techniques
- LIM-Homeodomain Proteins/genetics
- LIM-Homeodomain Proteins/physiology
- Nerve Growth Factors/antagonists & inhibitors
- Nerve Growth Factors/genetics
- Nerve Growth Factors/physiology
- Chromosomes, Artificial, Bacterial/genetics
- Animals, Genetically Modified
- Transcription Factors/genetics
- Transcription Factors/physiology
- Luminescent Proteins/genetics
- Luminescent Proteins/metabolism
- Receptors, Cell Surface/antagonists & inhibitors
- Receptors, Cell Surface/genetics
- Receptors, Cell Surface/physiology*
- Recombinant Proteins/genetics
- Recombinant Proteins/metabolism
- Prosencephalon/cytology
- Prosencephalon/embryology*
- Tumor Suppressor Proteins/antagonists & inhibitors
- Tumor Suppressor Proteins/genetics
- Tumor Suppressor Proteins/physiology
- Neurons/cytology
- DNA Primers/genetics
- 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.