Expression of genes in the16p11.2locus during human fetal cortical neurogenesis

Abstract

AbstractThe 593 kbp16p11.2copy number variation (CNV) affects the gene dosage of 29 protein coding genes, with heterozygous16p11.2microduplication or microdeletion implicated in about 1% of autism spectrum disorder (ASD) cases. The16p11.2CNV is frequently associated with macrocephaly or microcephaly indicating early defects of neurogenesis may contribute to subsequent ASD symptoms, but it is unknown which16p11.2transcripts are expressed in progenitors and whose levels are likely, therefore, to influence neurogenesis. Analysis of human fetal gene expression data revealed that of all the16p11.2transcripts only two,ALDOAandKIF22, are significantly enriched in progenitors. To investigate the role ofALDOAandKIF22in human cerebral cortex development we used immunohistochemical staining to describe their expression in late first and early second trimester human cerebral cortex. KIF22 protein is restricted to proliferating cells with its levels increasing during the cell cycle and peaking at mitosis. ALDOA protein is expressed in all cell types and does not vary with cell-cycle phase. Our expression analysis suggests the hypothesis that the simultaneous changes in KIF22 and ALDOA dosage in cortical progenitors causes defects in neurogenesis that may contribute to ASD in16p11.2CNV patients.