Open AccessHeat shock factor 2 is a stress‐responsive mediator of neuronal migration defects in models of fetal alcohol syndrome
Author(s) -
El Fatimy Rachid,
Miozzo Federico,
Mouël Anne,
Abane Ryma,
Schwendimann Leslie,
SabéranDjoneidi Délara,
Thonel Aurélie,
Massaoudi Illiasse,
Paslaru Liliana,
HashimotoTorii Kazue,
Christians Elisabeth,
Rakic Pasko,
Gressens Pierre,
Mezger Valérie
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201303311
Subject(s) - hsf1 , heat shock protein , mediator , microbiology and biotechnology , fetal alcohol syndrome , heat shock factor , fetus , hsp70 , biology , chemistry , alcohol , endocrinology , gene , biochemistry , genetics , pregnancy
Fetal alcohol spectrum disorder ( FASD ) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal and Hsf2 ‐deficient mice and cell systems to uncover a pivotal role for heat shock factor 2 ( HSF 2) in radial neuronal migration defects in the cortex, a hallmark of fetal alcohol exposure. Upon fetal alcohol exposure, HSF 2 is essential for the triggering of HSF 1 activation, which is accompanied by distinctive post‐translational modifications, and HSF 2 steers the formation of atypical alcohol‐specific HSF 1– HSF 2 heterocomplexes. This perturbs the in vivo binding of HSF 2 to heat shock elements ( HSE s) in genes that control neuronal migration in normal conditions, such as p35 or the MAP s (microtubule‐associated proteins , such as Dclk1 and Dcx ), and alters their expression. In the absence of HSF 2, migration defects as well as alterations in gene expression are reduced. Thus, HSF 2, as a sensor for alcohol stress in the fetal brain, acts as a mediator of the neuronal migration defects associated with FASD .