Abstract:
: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 (HSF2) in radial neuronal migration defects in the cortex, a hallmark of fetal alcohol exposure. Upon fetal alcohol exposure, HSF2 is essential for the triggering of HSF1 activation, which is accompanied by distinctive post-translational modifications, and HSF2 steers the formation of atypical alcohol-specific HSF1-HSF2 heterocomplexes. This perturbs the in vivo binding of HSF2 to heat shock elements (HSEs) in genes that control neuronal migration in normal conditions, such as p35 or the MAPs (microtubule-associated proteins, such as Dclk1 and Dcx), and alters their expression. In the absence of HSF2, migration defects as well as alterations in gene expression are reduced. Thus, HSF2, as a sensor for alcohol stress in the fetal brain, acts as a mediator of the neuronal migration defects associated with FASD.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
El Fatimy R,Miozzo F,Le Mouël A,Abane R,Schwendimann L,Sabéran-Djoneidi D,de Thonel A,Massaoudi I,Paslaru L,Hashimoto-Torii K,Christians E,Rakic P,Gressens P,Mezger Vdoi
10.15252/emmm.201303311subject
Has Abstractpub_date
2014-08-01 00:00:00pages
1043-61issue
8eissn
1757-4676issn
1757-4684pii
emmm.201303311journal_volume
6pub_type
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