Universität zu Köln

Pancho, Anna, Mitsogiannis, Manuela D. D., Aerts, Tania, Dalla Vecchia, Marco, Ebert, Lena K. K., Geenen, Lieve, Noterdaeme, Lut, Vanlaer, Ria, Stulens, Anne, Hulpiau, Paco, Staes, Katrien, Van Roy, Frans, Dedecker, Peter, Schermer, Bernhard and Seuntjens, Eve (2022). Modifying PCDH19 levels affects cortical interneuron migration. Front. Neurosci., 16. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1662-453X

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Abstract

PCDH19 is a transmembrane protein and member of the protocadherin family. It is encoded by the X-chromosome and more than 200 mutations have been linked to the neurodevelopmental PCDH-clustering epilepsy (PCDH19-CE) syndrome. A disturbed cell-cell contact that arises when random X-inactivation creates mosaic absence of PCDH19 has been proposed to cause the syndrome. Several studies have shown roles for PCDH19 in neuronal proliferation, migration, and synapse function, yet most of them have focused on cortical and hippocampal neurons. As epilepsy can also be caused by impaired interneuron migration, we studied the role of PCDH19 in cortical interneurons during embryogenesis. We show that cortical interneuron migration is affected by altering PCDH19 dosage by means of overexpression in brain slices and medial ganglionic eminence (MGE) explants. We also detect subtle defects when PCDH19 expression was reduced in MGE explants, suggesting that the dosage of PCDH19 is important for proper interneuron migration. We confirm this finding in vivo by showing a mild reduction in interneuron migration in heterozygote, but not in homozygote PCDH19 knockout animals. In addition, we provide evidence that subdomains of PCDH19 have a different impact on cell survival and interneuron migration. Intriguingly, we also observed domain-dependent differences in migration of the non-targeted cell population in explants, demonstrating a non-cell-autonomous effect of PCDH19 dosage changes. Overall, our findings suggest new roles for the extracellular and cytoplasmic domains of PCDH19 and support that cortical interneuron migration is dependent on balanced PCDH19 dosage.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pancho, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Mitsogiannis, Manuela D. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Aerts, Tania UNSPECIFIED UNSPECIFIED UNSPECIFIED Dalla Vecchia, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Ebert, Lena K. K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Geenen, Lieve UNSPECIFIED UNSPECIFIED UNSPECIFIED Noterdaeme, Lut UNSPECIFIED UNSPECIFIED UNSPECIFIED Vanlaer, Ria UNSPECIFIED UNSPECIFIED UNSPECIFIED Stulens, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Hulpiau, Paco UNSPECIFIED UNSPECIFIED UNSPECIFIED Staes, Katrien UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Roy, Frans UNSPECIFIED UNSPECIFIED UNSPECIFIED Dedecker, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Seuntjens, Eve UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-685447
DOI:	10.3389/fnins.2022.887478
Journal or Publication Title:	Front. Neurosci.
Volume:	16
Date:	2022
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1662-453X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-CELL ADHESION; N-CADHERIN; EPILEPSY; PROTOCADHERIN-19; CLEAVAGE; FEMALES; ENCEPHALOPATHY; IDENTIFICATION; EXPRESSION; MUTATIONS Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68544