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
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 19.912
Times Cited 60
Zebrafish rw0 (Tg(CM-isl1:GFP))?