Jacox Laura, Sindelka Radek, Chen Justin, Rothman Alyssa, Dickinson Amanda, Sive Hazel
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA; Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, USA; Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA; Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA; Harvard Graduate School of Arts and Sciences, 1350 Massachusetts Avenue, Holyoke Center, 50, Cambridge, MA 02138, USA.
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Cell Rep. 2014 Jul 24;8(2):596-609. doi: 10.1016/j.celrep.2014.06.026. Epub 2014 Jul 17.
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.
极前区(EAD)是一个保守的胚胎区域,包括预定的口部。我们发现激肽-激肽释放酶途径在EAD中活跃,并且对非洲爪蟾和斑马鱼的颅面发育至关重要。在该途径基因kng(编码缓激肽(xBdk))、羧肽酶-N(cpn,可裂解缓激肽)和神经元型一氧化氮合酶(nNOS)功能丧失(LOF)后,口部无法形成,神经嵴(NC)的发育和迁移也出现异常。与一氧化氮(NO)在面部形成中的作用一致,在途径基因功能丧失后内源性NO水平下降,但在将xBdk珠粒植入功能丧失胚胎的中部后,这些水平得以恢复且形成了正常的面部。面部移植表明,EAD内的Cpn功能对于第一鳃弓颅神经嵴向面部的迁移以及促进张口是必需的。该研究确定EAD是一个通过激肽-激肽释放酶信号起作用的重要颅面组织者。