TY - JOUR
T1 - N-cadherin (Cdh2) Maintains Migration and Postmitotic Survival of Cortical Interneuron Precursors in a Cell-Type-Specific Manner
AU - László, Zsófia I.
AU - Bercsényi, Kinga
AU - Mayer, Mátyás
AU - Lefkovics, Kornél
AU - Szabó, Gábor
AU - Katona, István
AU - Lele, Zsolt
N1 - Funding Information:
Hungarian Scientific Research Fund (OTKA, F 68177 to Z.L.); the European Research Council Grant (243153 to I.K.); the National Research, Development and Innovation Office, Hungary (VKSZ_14-1-2O15-0155 to I.K.); the Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002 to I.K.); the Hungarian Scientific Research Fund (OTKA, K 116915 to I.K.); the Momentum Program of the Hungarian Academy of Sciences (LP2013-54/2013 to I.K.); the Wellcome Trust International Senior Research Fellowship (090946/Z/09/Z to I.K.); Semmelweis University Predoctoral Grant (EFOP-3.6.3-VEKOP-16-2017-00009 to Z.I.L.); the Swiss Contribution grant (SH/7/2/18 to I.K.).
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/14
Y1 - 2020/3/14
N2 - The multiplex role of cadherin-based adhesion complexes during development of pallial excitatory neurons has been thoroughly characterized. In contrast, much less is known about their function during interneuron development. Here, we report that conditional removal of N-cadherin (Cdh2) from postmitotic neuroblasts of the subpallium results in a decreased number of Gad65-GFP-positive interneurons in the adult cortex. We also found that interneuron precursor migration into the pallium was already delayed at E14. Using immunohistochemistry and TUNEL assay in the embryonic subpallium, we excluded decreased mitosis and elevated cell death as possible sources of this defect. Moreover, by analyzing the interneuron composition of the adult somatosensory cortex, we uncovered an unexpected interneuron-type-specific defect caused by Cdh2-loss. This was not due to a fate-switch between interneuron populations or altered target selection during migration. Instead, potentially due to the migration delay, part of the precursors failed to enter the cortical plate and consequently got eliminated at early postnatal stages. In summary, our results indicate that Cdh2-mediated interactions are necessary for migration and survival during the postmitotic phase of interneuron development. Furthermore, we also propose that unlike in pallial glutamatergic cells, Cdh2 is not universal, rather a cell type-specific factor during this process.
AB - The multiplex role of cadherin-based adhesion complexes during development of pallial excitatory neurons has been thoroughly characterized. In contrast, much less is known about their function during interneuron development. Here, we report that conditional removal of N-cadherin (Cdh2) from postmitotic neuroblasts of the subpallium results in a decreased number of Gad65-GFP-positive interneurons in the adult cortex. We also found that interneuron precursor migration into the pallium was already delayed at E14. Using immunohistochemistry and TUNEL assay in the embryonic subpallium, we excluded decreased mitosis and elevated cell death as possible sources of this defect. Moreover, by analyzing the interneuron composition of the adult somatosensory cortex, we uncovered an unexpected interneuron-type-specific defect caused by Cdh2-loss. This was not due to a fate-switch between interneuron populations or altered target selection during migration. Instead, potentially due to the migration delay, part of the precursors failed to enter the cortical plate and consequently got eliminated at early postnatal stages. In summary, our results indicate that Cdh2-mediated interactions are necessary for migration and survival during the postmitotic phase of interneuron development. Furthermore, we also propose that unlike in pallial glutamatergic cells, Cdh2 is not universal, rather a cell type-specific factor during this process.
KW - cell death
KW - interneuron development
KW - mouse
KW - N-cadherin
KW - somatosensory cortex
UR - http://www.scopus.com/inward/record.url?scp=85083041972&partnerID=8YFLogxK
U2 - 10.1093/cercor/bhz168
DO - 10.1093/cercor/bhz168
M3 - Article
C2 - 31402374
AN - SCOPUS:85083041972
SN - 1047-3211
VL - 30
SP - 1318
EP - 1329
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 3
ER -