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Reversibility and developmental neuropathology of linear nevus sebaceous syndrome caused by dysregulation of the RAS pathway SCIE SCOPUS

Title
Reversibility and developmental neuropathology of linear nevus sebaceous syndrome caused by dysregulation of the RAS pathway
Authors
Kim, Ye EunKim, Yong-SeokLee, Hee-EunSo, Ki HurnChoe, YoungshikSuh, Byung-ChangKim, Joung-HunPark, Sang KiMathern, Gary W.Gleeson, Joseph G.Rah, Jong-CheolBaek, Seung Tae
Date Issued
2023-01
Publisher
Elsevier B.V.
Abstract
© 2023 The Author(s)Linear nevus sebaceous syndrome (LNSS) is a neurocutaneous disorder caused by somatic gain-of-function mutations in KRAS or HRAS. LNSS brains have neurodevelopmental defects, including cerebral defects and epilepsy; however, its pathological mechanism and potentials for treatment are largely unclear. We show that introduction of KRASG12V in the developing mouse cortex results in subcortical nodular heterotopia and enhanced excitability, recapitulating major pathological manifestations of LNSS. Moreover, we show that decreased firing frequency of inhibitory neurons without KRASG12V expression leads to disrupted excitation and inhibition balance. Transcriptional profiling after destabilization domain-mediated clearance of KRASG12V in human neural progenitors and differentiating neurons identifies reversible functional networks underlying LNSS. Neurons expressing KRASG12V show molecular changes associated with delayed neuronal maturation, most of which are restored by KRASG12V clearance. These findings provide insights into the molecular networks underlying the reversibility of some of the neuropathologies observed in LNSS caused by dysregulation of the RAS pathway.
URI
https://oasis.postech.ac.kr/handle/2014.oak/115089
DOI
10.1016/j.celrep.2023.112003
ISSN
2211-1247
Article Type
Article
Citation
Cell Reports, vol. 42, no. 1, 2023-01
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김정훈KIM, JOUNG HUN
Dept of Life Sciences
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