| RRC ID |
12136
|
| Author |
Fassier C, Hutt JA, Scholpp S, Lumsden A, Giros B, Nothias F, Schneider-Maunoury S, Houart C, Hazan J.
|
| Title |
Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway.
|
| Journal |
Nat Neurosci
|
| Abstract |
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.
|
| Volume |
13(11)
|
| Pages |
1380-7
|
| Published |
2010-11-1
|
| DOI |
10.1038/nn.2662
|
| PII |
nn.2662
|
| PMID |
20935645
|
| MeSH |
Animals
Animals, Genetically Modified
Axons / physiology*
Behavior, Animal
Bone Morphogenetic Proteins / genetics
Bone Morphogenetic Proteins / metabolism*
Cell Movement / physiology*
Cells, Cultured
Embryo, Nonmammalian
Endosomes / metabolism
Gene Expression Regulation, Developmental / genetics
Glycoproteins / genetics
Green Fluorescent Proteins / genetics
Intercellular Signaling Peptides and Proteins / genetics
Larva
Motor Neurons / cytology*
RNA, Messenger / physiology
Signal Transduction / genetics
Signal Transduction / physiology*
Spinal Cord / cytology*
Transcription Factors / genetics
Transcription Factors / metabolism
Tubulin / metabolism
Zebrafish
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism
|
| IF |
20.071
|
| Times Cited |
76
|
|
WOS Category
|
NEUROSCIENCES
|
| Resource |
| Zebrafish |
rw0 (Tg(CM-isl1:GFP))? |
