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CDH11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit

ABSTRACT: The molecular etiology of numerous risk genes for autism spectrum disorder (ASD), including CDH11, remains elusive. We investigated the role of CDH11 in the development of ASD-related behaviors using gene-deficient mice. CDH11 is enriched at synapses in glutamatergic neurons of the anterior cingulate cortex (ACC), which project to the striatum, nucleus accumbens, and amygdala. Ablation of Cdh11 in these neurons during development increases self-grooming and reduces sociability, with decreased neuronal activity in the ACC. Chemogenetic inhibition of ACC glutamatergic neurons recapitulates the over-grooming phenotype, while activation of these neurons mitigates self-grooming in Cdh11-deficient mice. Proteomics of ACC synaptosomes and CDH11 interactomes suggest the involvement of CDH11 in synaptic vesicle trafficking, supported by reduced presynaptic vesicle density at excitatory synapses in Cdh11-deficient mice. These findings highlight the critical role of CDH11 in ASD-related brain circuit development and offer insights into the molecular mechanisms and potential therapeutic targets for ASD

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Li Ze

LAB HEAD: Xiao-Bing Yuan

PROVIDER: PXD056411 | Pride | 2025-08-08

REPOSITORIES: Pride

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			Action	DRS
	Results.zip	Other
	XB02459DA_KO2_D4_1_30102.d.zip	Other
	XB02459DA_KO3_D5_1_30103.d.zip	Other
	XB02459DA_KO4_D6_1_30104.d.zip	Other
	XB02459DA_WT1_D1_1_30098.d.zip	Other

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CDH11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit

Project description:The molecular etiology of numerous risk genes for autism spectrum disorder (ASD), including CDH11, remains elusive. We investigated the role of CDH11 in the development of ASD-related behaviors using gene-deficient mice. CDH11 is enriched at synapses in glutamatergic neurons of the anterior cingulate cortex (ACC), which project to the striatum, nucleus accumbens, and amygdala. Ablation of Cdh11 in these neurons during development increases self-grooming and reduces sociability, with decreased neuronal activity in the ACC. Chemogenetic inhibition of ACC glutamatergic neurons recapitulates the over-grooming phenotype, while activation of these neurons mitigates self-grooming in Cdh11-deficient mice. Proteomics of ACC synaptosomes and CDH11 interactomes suggest the involvement of CDH11 in synaptic vesicle trafficking, supported by reduced presynaptic vesicle density at excitatory synapses in Cdh11-deficient mice. These findings highlight the critical role of CDH11 in ASD-related brain circuit development and offer insights into the molecular mechanisms and potential therapeutic targets for ASD.

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CDH11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit

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