Skip to Main content Skip to Navigation
Journal articles

Pax3 and Pax7 Play Essential Safeguard Functions against Environmental Stress-Induced Birth Defects

Abstract : Exposure to environmental teratogenic pollutant leads to severe birth defects. However, the biological events underlying these developmental abnormalities remain undefined. Here, we report a molecular link between an environmental stress response pathway and key developmental genes during craniofacial development. Strikingly, mutant mice with impaired Pax3/7 function display severe craniofacial defects. We show that these are associated with an upregulation of the signaling pathway mediated by the Aryl hydrocarbon receptor (AHR), the receptor to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), revealing a genetic interaction between Pax3 and AHR signaling. Activation of AHR signaling in Pax3-deficient embryos drives facial mesenchymal cells out of the cell cycle through the upregulation of p21 expression. Accordingly, inhibiting AHR activity rescues the cycling status of these cells and the facial closure of Pax3/7 mutants. Together, our findings demonstrate that the regulation of AHR signaling by Pax3/7 is required to protect against TCDD/AHR-mediated teratogenesis during craniofacial development.
Document type :
Journal articles
Complete list of metadatas

Cited literature [66 references]  Display  Hide  Download

https://hal.sorbonne-universite.fr/hal-01140302
Contributor : Administrateur Hal-Upmc <>
Submitted on : Wednesday, April 8, 2015 - 12:12:17 PM
Last modification on : Tuesday, December 15, 2020 - 3:28:16 AM
Long-term archiving on: : Thursday, July 9, 2015 - 10:15:12 AM

File

Zalc_Pax3_and_Pax7_Play.pdf
Files produced by the author(s)

Identifiers

Citation

Antoine Zalc, Revital Rattenbach, Frédéric Auradé, Bruno Cadot, Frédéric Relaix. Pax3 and Pax7 Play Essential Safeguard Functions against Environmental Stress-Induced Birth Defects. Developmental Cell, Elsevier, 2015, 33 (1), pp.56-66. ⟨10.1016/j.devcel.2015.02.006⟩. ⟨hal-01140302⟩

Share

Metrics

Record views

399

Files downloads

443