Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity
| العنوان: | Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity |
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| المؤلفون: | Christopher J. Bott, Colin Johnson, K. A. Litwa, Noelle D. Dwyer, Chan Choo Yap, Bettina Winckler |
| المصدر: | Molecular Biology of the Cell |
| بيانات النشر: | The American Society for Cell Biology, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Growth Cones, Induced Pluripotent Stem Cells, Primary Cell Culture, macromolecular substances, Biology, Axonal growth cone, Nestin, 03 medical and health sciences, Mice, 0302 clinical medicine, Neural Stem Cells, Ganglia, Spinal, medicine, Animals, Humans, Phosphorylation, Growth cone, Molecular Biology, reproductive and urinary physiology, Cytoskeleton, Embryonic Stem Cells, 030304 developmental biology, Neurons, 0303 health sciences, Neocortex, Cyclin-dependent kinase 5, SEMA3A, Semaphorin-3A, Cell Biology, Articles, Axons, Cell biology, medicine.anatomical_structure, HEK293 Cells, nervous system, embryonic structures, Axon guidance, Female, Neuron, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | Correct wiring in the neocortex requires that responses to an individual guidance cue vary among neurons in the same location, and within the same neuron over time. Nestin is an atypical intermediate filament expressed strongly in neural progenitors and is thus used widely as a progenitor marker. Here we show a subpopulation of embryonic cortical neurons that transiently express nestin in their axons. Nestin expression is thus not restricted to neural progenitors, but persists for 2–3 d at lower levels in newborn neurons. We found that nestin-expressing neurons have smaller growth cones, suggesting that nestin affects cytoskeletal dynamics. Nestin, unlike other intermediate filament subtypes, regulates cdk5 kinase by binding the cdk5 activator p35. Cdk5 activity is induced by the repulsive guidance cue Semaphorin3a (Sema3a), leading to axonal growth cone collapse in vitro. Therefore, we tested whether nestin-expressing neurons showed altered responses to Sema3a. We find that nestin-expressing newborn neurons are more sensitive to Sema3a in a roscovitine-sensitive manner, whereas nestin knockdown results in lowered sensitivity to Sema3a. We propose that nestin functions in immature neurons to modulate cdk5 downstream of the Sema3a response. Thus, the transient expression of nestin could allow temporal and/or spatial modulation of a neuron’s response to Sema3a, particularly during early axon guidance. |
| اللغة: | English |
| تدمد: | 1939-4586 1059-1524 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e01f730be7bbb563263e568b02e3d4aTest http://europepmc.org/articles/PMC6724523Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3e01f730be7bbb563263e568b02e3d4a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19394586 10591524 |
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