Semaphorin-3A guides radial migration of cortical neurons during development.
Postmitotic neurons in the developing cortex migrate along radial glial fibers to their proper location in the cortical plate and form the layered structure. Here we report that the radial migration of rat layer II/III cortical neurons requires guidance by the extracellular diffusible factor Semaphorin-3A (Sema3A). This factor is expressed in a descending gradient across the cortical layers, whereas its receptor neuropilin-1 (NP1) is highly expressed in migrating neurons. Downregulation or conditional knockout of NP1 in newborn cortical neurons impedes their radial migration by disrupting their radial orientation during migration without altering their cell fate. Studies in cultured cortical slices further show that the endogenous gradient of Sema3A is required for the proper migration of newborn neurons. In addition, transwell chemotaxis assays show that isolated newborn neurons are attracted by Sema3A. Thus, Sema3A may function as a chemoattractive guidance signal for the radial migration of newborn cortical neurons toward upper layers.
Chen
Gang
G
Institute of Neuroscience and Key State Laboratory of Neurobiology, Shanghai Institute for Biological Sciences, Shanghai, China.
Sima
Jian
J
Jin
Ming
M
Wang
Kai-Yu
KY
Xue
Xiao-Jing
XJ
Zheng
Wang
W
Ding
Yu-Qiang
YQ
Yuan
Xiao-Bing
XB
D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics; D054443:Cell Migration Assays; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D004305:Dose-Response Relationship, Drug; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000502:physiology*; D039942:Neuropilin-1 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D040121:Semaphorin-3A / Q000235:genetics / Q000502:physiology*
D001426:Bacterial Proteins; D008164:Luminescent Proteins; D034741:RNA, Small Interfering; D040121:Semaphorin-3A; C054562:yellow fluorescent protein, Bacteria; D039942:Neuropilin-1