Helmholtz Gemeinschaft


Cdon mutation and fetal alcohol converge on Nodal signaling in a mouse model of holoprosencephaly

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader

Item Type:Article
Title:Cdon mutation and fetal alcohol converge on Nodal signaling in a mouse model of holoprosencephaly
Creators Name:Hong, M. and Christ, A. and Christa, A. and Willnow, T.E. and Krauss, R.S.
Abstract:Holoprosencephaly (HPE), a defect in midline patterning of the forebrain and midface, arises ~1 in 250 conceptions. It is associated with predisposing mutations in the Nodal and Hedgehog (HH) pathways, with penetrance and expressivity graded by genetic and environmental modifiers, via poorly understood mechanisms. CDON is a multifunctional co-receptor, including for the HH pathway. In mice, Cdon mutation synergizes with fetal alcohol exposure, producing HPE phenotypes closely resembling those seen in humans. We report here that, unexpectedly, Nodal signaling is a major point of synergistic interaction between Cdon mutation and fetal alcohol. Window-of-sensitivity, genetic, and in vitro findings are consistent with a model whereby brief exposure of Cdon mutant embryos to ethanol during gastrulation transiently and partially inhibits Nodal pathway activity, with consequent effects on midline patterning. These results illuminate mechanisms of gene-environment interaction in a multifactorial model of a common birth defect.
Keywords:Holoprosencephaly, Fetal Alcohol, Birth Defect, Nodal Signaling, Hedgehog Signaling, Gene-Environment Interaction, Animals, Mice
Publisher:eLife Sciences Publications
Page Range:e60351
Date:2 September 2020
Official Publication:https://doi.org/10.7554/eLife.60351
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library