The Extreme Anterior Domain Is an Essential Craniofacial Organizer Acting through Kinin-Kallikrein Signaling
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Author(s)
Sindelka, Radek
Chen, Justin
Rothman, Alyssa
Dickinson, Amanda J.
Jacox, Laura A.
Sive, Hazel L.
Date Issued
July 2014
Journal
Cell Reports
Publisher
Elsevier
Citation
Jacox, Laura, Radek Sindelka, Justin Chen, Alyssa Rothman, Amanda Dickinson, and Hazel Sive. “The Extreme Anterior Domain Is an Essential Craniofacial Organizer Acting through Kinin-Kallikrein Signaling.” Cell Reports 8, no. 2 (July 2014): 596–609.
Version
Final published version
Abstract
The extreme anterior domain (EAD) is a conserved embryonic region that includes the presumptive mouth. We show that the Kinin-Kallikrein pathway is active in the EAD and necessary for craniofacial development in Xenopus and zebrafish. The mouth failed to form and neural crest (NC) development and migration was abnormal after loss of function (LOF) in the pathway genes kng, encoding Bradykinin (xBdk), carboxypeptidase-N (cpn), which cleaves Bradykinin, and neuronal nitric oxide synthase (nNOS). Consistent with a role for nitric oxide (NO) in face formation, endogenous NO levels declined after LOF in pathway genes, but these were restored and a normal face formed after medial implantation of xBdk-beads into LOF embryos. Facial transplants demonstrated that Cpn function from within the EAD is necessary for the migration of first arch cranial NC into the face and for promoting mouth opening. The study identifies the EAD as an essential craniofacial organizer acting through Kinin-Kallikrein signaling.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2014.06.026
