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Osmotic avoidance in Caenorhabditis elegans: synaptic function of two genes, orthologues of human NRXN1 and NLGN1, as candidates for autism

Osmotic avoidance in Caenorhabditis elegans: synaptic function of two genes, orthologues of human NRXN1 and NLGN1, as candidates for autism
Osmotic avoidance in Caenorhabditis elegans: synaptic function of two genes, orthologues of human NRXN1 and NLGN1, as candidates for autism
Neurexins and neuroligins are cell adhesion molecules present in excitatory and inhibitory synapses, and they are required for correct neuron network function. These proteins are found at the presynaptic and postsynaptic membranes. Studies in mice indicate that neurexins and neurologins have an essential role in synaptic transmission. Recent reports have shown that altered neuronal connections during the development of the human nervous system could constitute the basis of the etiology of numerous cases of autism spectrum disorders. Caenorhabditis elegans could be used as an experimental tool to facilitate the study of the functioning of synaptic components, because of its simplicity for laboratory experimentation, and given that its nervous system and synaptic wiring has been fully characterized. In C. elegans nrx-1 and nlg-1 genes are orthologous to human NRXN1 and NLGN1 genes which encode alpha-neurexin-1 and neuroligin-1 proteins, respectively. In humans and nematodes, the organization of neurexins and neuroligins is similar in respect to functional domains. The head of the nematode contains the amphid, a sensory organ of the nematode, which mediates responses to different stimuli, including osmotic strength. The amphid is made of 12 sensory bipolar neurons with ciliated dendrites and one presynaptic terminal axon. Two of these neurons, named ASHR and ASHL are particularly important in osmotic sensory function, detecting water-soluble repellents with high osmotic strength. The dendrites of these two neurons lengthen to the tip of the mouth and the axons extend to the nerve ring, where they make synaptic connections with other neurons determining the behavioral response. To evaluate the implications of neurexin and neuroligin in high osmotic strength avoidance, we show the different response of C. elegans mutants defective in nrx-1 and nlg-1 genes, using a method based on a 4M fructose ring. The behavioral phenotypes were confirmed using specific RNAi clones. In C. elegans, the dsRNA required to trigger RNAi can be administered by feeding. The delivery of dsRNA through food induces the RNAi interference of the gene of interest thus allowing the identification of genetic components and network pathways
1940-087X
1616
Calahorro, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Alejandre, Encarna
f750362a-b09e-4eac-9e1b-dd124473d373
Ruiz-Rubio, Manuel
bb788f2e-5703-4b36-bd3e-1aa546997e61
Calahorro, Fernando
dddfa373-d3cc-433f-8851-9ca37f2f3950
Alejandre, Encarna
f750362a-b09e-4eac-9e1b-dd124473d373
Ruiz-Rubio, Manuel
bb788f2e-5703-4b36-bd3e-1aa546997e61

Calahorro, Fernando, Alejandre, Encarna and Ruiz-Rubio, Manuel (2009) Osmotic avoidance in Caenorhabditis elegans: synaptic function of two genes, orthologues of human NRXN1 and NLGN1, as candidates for autism. Journal of Visualized Experiments, 34, 1616. (doi:10.3791/1616). (PMID:20010541)

Record type: Article

Abstract

Neurexins and neuroligins are cell adhesion molecules present in excitatory and inhibitory synapses, and they are required for correct neuron network function. These proteins are found at the presynaptic and postsynaptic membranes. Studies in mice indicate that neurexins and neurologins have an essential role in synaptic transmission. Recent reports have shown that altered neuronal connections during the development of the human nervous system could constitute the basis of the etiology of numerous cases of autism spectrum disorders. Caenorhabditis elegans could be used as an experimental tool to facilitate the study of the functioning of synaptic components, because of its simplicity for laboratory experimentation, and given that its nervous system and synaptic wiring has been fully characterized. In C. elegans nrx-1 and nlg-1 genes are orthologous to human NRXN1 and NLGN1 genes which encode alpha-neurexin-1 and neuroligin-1 proteins, respectively. In humans and nematodes, the organization of neurexins and neuroligins is similar in respect to functional domains. The head of the nematode contains the amphid, a sensory organ of the nematode, which mediates responses to different stimuli, including osmotic strength. The amphid is made of 12 sensory bipolar neurons with ciliated dendrites and one presynaptic terminal axon. Two of these neurons, named ASHR and ASHL are particularly important in osmotic sensory function, detecting water-soluble repellents with high osmotic strength. The dendrites of these two neurons lengthen to the tip of the mouth and the axons extend to the nerve ring, where they make synaptic connections with other neurons determining the behavioral response. To evaluate the implications of neurexin and neuroligin in high osmotic strength avoidance, we show the different response of C. elegans mutants defective in nrx-1 and nlg-1 genes, using a method based on a 4M fructose ring. The behavioral phenotypes were confirmed using specific RNAi clones. In C. elegans, the dsRNA required to trigger RNAi can be administered by feeding. The delivery of dsRNA through food induces the RNAi interference of the gene of interest thus allowing the identification of genetic components and network pathways

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Published date: December 2009
Organisations: Biomedicine

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Local EPrints ID: 366697
URI: https://eprints.soton.ac.uk/id/eprint/366697
ISSN: 1940-087X
PURE UUID: 3cc7a021-eb11-4d87-b3ed-2673e87930b2
ORCID for Fernando Calahorro: ORCID iD orcid.org/0000-0003-0659-7728

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Date deposited: 10 Jul 2014 11:15
Last modified: 06 Jun 2018 12:25

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