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Cell Rep 2014 Jul 24;82:596-609. doi: 10.1016/j.celrep.2014.06.026.
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The extreme anterior domain is an essential craniofacial organizer acting through Kinin-Kallikrein signaling.

Jacox L , Sindelka R , Chen J , Rothman A , Dickinson A , Sive H .

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.

PubMed ID: 25043181
PMC ID: PMC4135435
Article link: Cell Rep
Grant support: [+]

Species referenced: Xenopus
Genes referenced: bdkrb2 cpn1 ctnnb1 des.1 des.2 frzb hesx1 klk1 kng1 mark3 muc2 nos1 nos3 snai2 sox10 sox9 tbx2
Morpholinos: cpn1 MO1 kng1 MO1 kng1 MO2 nos1 MO1

Disease Ontology terms: dental abscess

Article Images: [+] show captions
References [+] :
Aoki, Sox10 regulates the development of neural crest-derived melanocytes in Xenopus. 2003, Pubmed, Xenbase