Lewis, Philip Alexander, Bradley, Isobel Claire, Pizzey, Alastair Robert et al. (2 more authors) (2017) N1-Src kinase is required for primary neurogenesis in Xenopus tropicalis. Journal of neuroscience. pp. 8477-8584. ISSN 1529-2401
Abstract
The presence of the neuronal-specific N1-Src splice variant of the C-Src tyrosine kinase is conserved through vertebrate evolution, suggesting an important role in complex nervous systems. Alternative splicing involving a N1-Src specific microexon leads to a five or six amino acid insertion into the SH3 domain of Src. A prevailing model suggests that N1-Src regulates neuronal differentiation via cytoskeletal dynamics in the growth cone. Here we have investigated the role of n1-src in the early development of the amphibian Xenopus tropicalis, and find that n1-src expression is regulated in embryogenesis, with highest levels detected during the phases of primary and secondary neurogenesis. In situ hybridisation analysis, using locked nucleic acid (LNA) oligo probes complementary to the n1-src microexon indicate that n1-src expression is highly enriched in the open neural plate during neurula stages and in the neural tissue of adult frogs. Given the n1-src expression pattern, we investigated a possible role for n1-src in neurogenesis. Using splice site-specific antisense morpholino oligos, we are able to inhibit n1-src splicing, whilst preserving c-src expression. Differentiation of neurons in the primary nervous system is reduced in n1-src knockdown embryos, accompanied by a severely impaired touch response in later development. These data reveal an essential role for n1-src in amphibian neural development and suggest that alternative splicing of C-Src in the developing vertebrate nervous system evolved to regulate neurogenesis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Lewis, Bradley et al. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 31 Aug 2017 10:00 |
Last Modified: | 08 Feb 2025 00:23 |
Published Version: | https://doi.org/10.1523/JNEUROSCI.3881-16.2017 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1523/JNEUROSCI.3881-16.2017 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:120722 |
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