title: Atlastin-1 regulates dendritic morphogenesis in mouse cerebral cortex.
abstract: Hereditary spastic paraplegias (HSPs) are human genetic disorders characterized by lower extremity spasticity and weakness. Mutations in atlastin-1 (ATL1) have been identified in patients with HSP SPG3A. However, the function of ATL1 in the mammalian brain remains unclear. Here, we found that expression of ATL1 mRNA was restricted in the deep layer of mouse cerebral cortex during the early development. We examined ATL1 functions by delivering its plasmids to the upper layer cortical neurons using in utero electroporation. The effects of ectopic expression in the pyramidal neurons were determined both in culture and in situ at postnatal stages of neocortical development. In cultured cortical neurons, overexpressing ATL1 increased dendrite growth and arborization, whereas HSP-associated mutant R217Q, which is devoid of GTPase activity, had no such effects. Consistent with this, in vivo expression of wild type ATL1, but not of the mutant R217Q, increased dendritic growth of the cortical neurons. This suggests that the role of ATL1 on dendritic morphogenesis depends on its GTPase activity. The expression of ATL1 and R217Q did not affect the migration of cortical neurons. These results indicate that ATL1 regulates dendritic morphogenesis, which may provide new insights into the neuropathogenic mechanism of hereditary spastic paraplegia SPG3A.
authors.affiliation: Key Laboratory of Visual Science, National Ministry of Health and School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou 325027, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Tian
authors.initials: T
authors.lastname: Jiang
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Qu
authors.forename: Huaping
authors.initials: H
authors.lastname: Tao
authors.forename: Huateng
authors.initials: H
authors.lastname: Cao
authors.forename: Yuee
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.forename: Jie-Guang
authors.initials: JG
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009024:Morphogenesis; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D008565:Membrane Proteins; C000589974:ATL1 protein, mouse
keywords: Atlastin-1; Cerebral cortex; In utero electroporation; Migration; Neuronal morphogenesis