Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model
Copyright policy )Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model
Significance 22q11 deletion syndrome (22q11DS) is a chromosome disorder that frequently accompanies psychiatric conditions such as schizophrenia. However, it remains elusive how the chromosomal microdeletion causes the mental manifestation. Here we show that a 22q11DS mouse model has deficits in the development of interneurons and hippocampal dentate gyrus and that DiGeorge syndrome critical region gene 8 (Dgcr8) , a microprocessor of microRNA and one of the genes in 22q11, underlies these neurodevelopmental abnormalities. Dgcr8 regulates Chemokine receptor 4/Chemokine ligand 12 (Cxcr4/Cxcl12; Sdf1) signaling, which is indispensable for interneuron and dentate gyrus development. Finally, we observe decreased expression of CXCL12 in olfactory neurons from sporadic schizophrenia. Given the increased risk of 22q11DS in schizophrenia, the overall study suggests that CXCR4/CXCL12 signaling may represent a common downstream mediator in the pathophysiology of schizophrenia.
- Kyoto University Japan
- Università degli studi di Salerno Italy
- Johns Hopkins Medicine United States
- Johns Hopkins University School of Medicine United States
- Nara Medical University Japan
Mice, Knockout, Receptors, CXCR4, 22q11 Deletion Syndrome, Gene Expression Profiling, RNA-Binding Proteins, Immunohistochemistry, Chemokine CXCL12, Mice, Inbred C57BL, Disease Models, Animal, Gene Knockout Techniques, Mice, MicroRNAs, HEK293 Cells, Interneurons, Dentate Gyrus, Animals, Humans, Nervous System Diseases, Cells, Cultured, Oligonucleotide Array Sequence Analysis
Mice, Knockout, Receptors, CXCR4, 22q11 Deletion Syndrome, Gene Expression Profiling, RNA-Binding Proteins, Immunohistochemistry, Chemokine CXCL12, Mice, Inbred C57BL, Disease Models, Animal, Gene Knockout Techniques, Mice, MicroRNAs, HEK293 Cells, Interneurons, Dentate Gyrus, Animals, Humans, Nervous System Diseases, Cells, Cultured, Oligonucleotide Array Sequence Analysis
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