X-linked diseases typically exhibit more severe phenotypes in males than females. In contrast, protocadherin 19 (PCDH19) mutations cause epilepsy in heterozygous females but spare hemizygous males. The cellular mechanism responsible for this unique pattern of X-linked inheritance is unknown. We show that PCDH19 contributes to adhesion specificity in a combinatorial manner such that mosaic expression of Pcdh19 in heterozygous female mice leads to striking sorting between cells expressing wild-type (WT) PCDH19 and null PCDH19 in the developing cortex, correlating with altered network activity. Complete deletion of PCDH19 in heterozygous mice abolishes abnormal cell sorting and restores normal network activity. Furthermore, we identify variable cortical malformations in PCDH19 epilepsy patients. Our results highlight the role of PCDH19 in determining cell adhesion affinities during cortical development and the way segregation of WT and null PCDH19 cells is associated with the unique X-linked inheritance of PCDH19 epilepsy.
Pubmed ID: 29301106 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets Ctip2
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets Human SOX3
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis polyclonal targets PCDH17
View all literature mentionsThis monoclonal targets Rat OL-protocadherin Clone 5G10
View all literature mentionsThis polyclonal targets β-actin
View all literature mentionsThis monoclonal targets PCDH19
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis polyclonal targets Myc-Tag
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsCell line K-562 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentions