Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway
- Fassier, C., Hutt, J.A., Scholpp, S., Lumsden, A., Giros, B., Nothias, F., Schneider-Maunoury, S., Houart, C., and Hazan, J.
- Nature Neuroscience 13(11): 1380-1387 (Journal)
- Registered Authors
- Hazan, Jamile, Houart, Corinne, Hutt, James, Lumsden, Andrew, Schneider-Maunoury, Sylvie, Scholpp, Steffen
- MeSH Terms
- Animals, Genetically Modified
- Behavior, Animal
- Bone Morphogenetic Proteins/genetics
- Bone Morphogenetic Proteins/metabolism*
- Cell Movement/physiology*
- Cells, Cultured
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/genetics
- Green Fluorescent Proteins/genetics
- Intercellular Signaling Peptides and Proteins/genetics
- Motor Neurons/cytology*
- RNA, Messenger/physiology
- Signal Transduction/genetics
- Signal Transduction/physiology*
- Spinal Cord/cytology*
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- 20935645 Full text @ Nat. Neurosci.
Fassier, C., Hutt, J.A., Scholpp, S., Lumsden, A., Giros, B., Nothias, F., Schneider-Maunoury, S., Houart, C., and Hazan, J. (2010) Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway. Nature Neuroscience. 13(11):1380-1387.
To better understand hereditary spastic paraplegia (HSP), we characterized the function of atlastin, a protein that is frequently involved in juvenile forms of HSP, by analyzing loss- and gain-of-function phenotypes in the developing zebrafish. We found that knockdown of the gene for atlastin (atl1) caused a severe decrease in larval mobility that was preceded by abnormal architecture of spinal motor axons and was associated with a substantial upregulation of the bone morphogenetic protein (BMP) signaling pathway. Overexpression analyses confirmed that atlastin inhibits BMP signaling. In primary cultures of zebrafish spinal neurons, Atlastin partially colocalized with type I BMP receptors in late endosomes distributed along neurites, which suggests that atlastin may regulate BMP receptor trafficking. Finally, genetic or pharmacological inhibition of BMP signaling was sufficient to rescue the loss of mobility and spinal motor axon defects of atl1 morphants, emphasizing the importance of fine-tuning the balance of BMP signaling for vertebrate motor axon architecture and stability.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes