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.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Delmotte Q,Hamze M,Medina I,Buhler E,Zhang J,Belgacem YH,Porcher Cdoi
10.1242/jcs.247700subject
Has Abstractpub_date
2020-10-23 00:00:00issue
20eissn
0021-9533issn
1477-9137pii
jcs.247700journal_volume
133pub_type
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