Using zebrafish to understand the neurodevelopment role of susceptibility genes for autism spectrum disorder

Key, B. (2010). Using zebrafish to understand the neurodevelopment role of susceptibility genes for autism spectrum disorder. In: Abstracts to the 18th Biennial Meeting of the International Society for Developmental Neuroscience. 18th Biennial Meeting of the International-Society-for-Developmental-Neuroscience, Estoril, Portugal, (686-687). 6-9 June 2010. doi:10.1016/j.ijdevneu.2010.07.134


Author Key, B.
Title of paper Using zebrafish to understand the neurodevelopment role of susceptibility genes for autism spectrum disorder
Conference name 18th Biennial Meeting of the International-Society-for-Developmental-Neuroscience
Conference location Estoril, Portugal
Conference dates 6-9 June 2010
Proceedings title Abstracts to the 18th Biennial Meeting of the International Society for Developmental Neuroscience   Check publisher's open access policy
Journal name International Journal of Developmental Neuroscience   Check publisher's open access policy
Place of Publication Oxford, United Kingdom
Publisher Pergamon
Publication Year 2010
Sub-type Published abstract
DOI 10.1016/j.ijdevneu.2010.07.134
ISSN 0736-5748
1873-474X
Volume 28
Issue 8
Start page 686
End page 687
Total pages 1
Language eng
Abstract/Summary Several studies in the last three years have revealed that members of a synaptic cell adhesion network are candidate susceptibility genes for Autism spectrum disorder (ASD). These genes include neurexin-1 (NRXN1), neuroligin-1 (NLGN1), NLGN4, contactin associated protein 2 (CNTNAP2 or previously known as CASPR2) and Shank3. ASD is increasingly attributed to a disorder of brain function rather than brain anatomy. We have begun to address the role of gene-gene interactions within the synaptic cell adhesion pathway involved in neural circuits associated with simple behaviours using the zebrafish animal model. We are focusing on interactions between identified susceptibility genes NLGN-1, NLGN-4, NRXN-1□, Shank3 and CNTNAP2 as well as on interactions of these genes with other known synaptic cell adhesion pathway genes (LRRTM2, PSD-95 and CASK) in order to begin to understand the function of gene networks underlying the emergence of early behaviours. We have generated morpholinos against NRXN-1a□, NRXN1b□ and CNTNAP2 and injected them individually into one cell embryos and then assessed the touch and escape responses at 30 and 45 h, respectively. Knock down of either NRXN-1a□, NRXN1b□ or CNTAP2 significantly reduced the touch response at 30 hpf to a similar extent. The high penetrance of these phenotypes (71–84%) suggest that these genes are playing a major role in the development of the underlying neural circuitry responsible for this behaviour. In contrast, at 45 hpf knock down of NRXN-1a□ had no effect on the escape response, knock down of NRXN1b□ either extinguished or reduced the response, while knock down of CNTNAP2 produced an abnormal response. These very different phenotypes suggest very different roles of these synaptic adhesion network genes in the underlying neural circuitry. Our analyses are beginning to reveal the most critical genes involved in development of neural circuits underlying a simple behaviour.
Keyword Zebrafish
Synapse
Behavior
Adhesion
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Available online 1 November 2010

Document type: Conference Paper
Collection: School of Biomedical Sciences Publications
 
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Created: Sun, 06 Feb 2011, 00:08:21 EST