Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17168
Title: Abnormal Cell Sorting Underlies the Unique X-Linked Inheritance of PCDH19 Epilepsy.
Authors: Pederick, Daniel T;Richards, Kay L;Piltz, Sandra G;Kumar, Raman;Mincheva-Tasheva, Stefka;Mandelstam, Simone A;Dale, Russell C;Scheffer, Ingrid E;Gecz, Jozef;Petrou, Steven;Hughes, James N;Thomas, Paul Q
Affiliation: School of Biological Sciences and Robinson Research Institute, The University of Adelaide, Adelaide, SA 5005, Australia
Florey Institute of Neuroscience and Mental Health and Department of Medicine Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC 3010, Australia
School of Medicine and Robinson Research Institute, The University of Adelaide, Adelaide, SA 5005, Australia
Department of Paediatrics, The University of Melbourne, Melbourne, VIC 3010, Australia
Department of Radiology, The University of Melbourne, Melbourne, VIC 3010, Australia
Department of Medical Imaging, Royal Children's Hospital, Florey Neurosciences Institute, Parkville, VIC 3052, Australia
Institute for Neuroscience and Muscle Research, University of Sydney, Sydney, NSW 2006, Australia
The University of Melbourne, Melbourne, VIC, Australia
South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
Royal Children's Hospital, Melbourne, VIC, Australia
Austin Health, Heidelberg, Victoria, Australia
Issue Date: 3-Jan-2018
Citation: Neuron 2018; 97(1): 59-66.e5
Abstract: 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17168
DOI: 10.1016/j.neuron.2017.12.005
ORCID: 0000-0002-2311-2174
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/29301106
Type: Journal Article
Subjects: PCDH19-GCE
adhesion molecules
cell sorting
cell-cell adhesion code
cortical development
epilepsy
protocadherin 19
protocadherins
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.