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Smoothened receptor signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex.

Authors
  • Delmotte, Quentin1, 2, 3
  • Hamze, Mira1, 2, 3
  • Medina, Igor1, 2, 3
  • Buhler, Emmanuelle2, 4
  • Zhang, Jinwei5
  • Belgacem, Yesser H2, 3
  • Porcher, Christophe6, 2, 3
  • 1 Aix-Marseille University, Parc Scientifique de Luminy, 13273, Marseille, France. , (France)
  • 2 INSERM (Institut National de la Santé et de la Recherche Médicale) Unité 1249, Marseille, Parc Scientifique de Luminy, 13273 Marseille, France. , (France)
  • 3 INMED (Institut de Neurobiologie de la Méditerranée), Parc Scientifique de Luminy, 13273 Marseille, France. , (France)
  • 4 Plateforme Post-Génomique, INMED, 13273 Marseille, France. , (France)
  • 5 Institute of Biomedical and Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, Hatherly Laboratories, Exeter EX4 4PS, UK.
  • 6 Aix-Marseille University, Parc Scientifique de Luminy, 13273, Marseille, France [email protected] , (France)
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Oct 23, 2020
Volume
133
Issue
20
Identifiers
DOI: 10.1242/jcs.247700
PMID: 32989040
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Sonic hedgehog (Shh) and its patched-smoothened receptor complex control a variety of functions in the developing central nervous system, such as neural cell proliferation and differentiation. Recently, Shh signaling components have been found to be expressed at the synaptic level in the postnatal brain, suggesting a potential role in the regulation of synaptic transmission. Using in utero electroporation of constitutively active and negative-phenotype forms of the Shh signal transducer smoothened (Smo), we studied the role of Smo signaling in the development and maturation of GABAergic transmission in the somatosensory cortex. Our results show that enhancing Smo activity during development accelerates the shift from depolarizing to hyperpolarizing GABA in a manner dependent on functional expression of potassium-chloride cotransporter type 2 (KCC2, also known as SLC12A5). On the other hand, blocking Smo activity maintains the GABA response in a depolarizing state in mature cortical neurons, resulting in altered chloride homeostasis and increased seizure susceptibility. This study reveals unexpected functions of Smo signaling in the regulation of chloride homeostasis, through control of KCC2 cell-surface stability, and the timing of the GABA excitatory-to-inhibitory shift in brain maturation. © 2020. Published by The Company of Biologists Ltd.

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