Bae Chang-Joon, Hong Chang-Soo, Saint-Jeannet Jean-Pierre
Department of Basic Science & Craniofacial Biology, College of Dentistry, New York University, New York, USA.
Department of Basic Science & Craniofacial Biology, College of Dentistry, New York University, New York, USA.
Biochem Biophys Res Commun. 2018 Jan 15;495(3):2257-2263. doi: 10.1016/j.bbrc.2017.12.127. Epub 2017 Dec 22.
During embryogenesis vertebrates develop a complex craniofacial skeleton associated with sensory organs. These structures are primarily derived from two embryonic cell populations the neural crest and cranial placodes, respectively. Neural crest cells and cranial placodes are specified through the integrated action of several families of signaling molecules, and the subsequent activation of a complex network of transcription factors. Here we describe the expression and function of Anosmin-1 (Anos1), an extracellular matrix protein, during neural crest and cranial placodes development in Xenopus laevis. Anos1 was identified as a target of Pax3 and Zic1, two transcription factors necessary and sufficient to generate neural crest and cranial placodes. Anos1 is expressed in cranial neural crest progenitors at early neurula stage and in cranial placode derivatives later in development. We show that Anos1 function is required for neural crest and sensory organs development in Xenopus, consistent with the defects observed in Kallmann syndrome patients carrying a mutation in ANOS1. These findings indicate that anos1 has a conserved function in the development of craniofacial structures, and indicate that anos1-depleted Xenopus embryos represent a useful model to analyze the pathogenesis of Kallmann syndrome.
在胚胎发育过程中,脊椎动物会发育出与感觉器官相关的复杂颅面骨骼。这些结构主要分别源自两个胚胎细胞群体,即神经嵴和颅基板。神经嵴细胞和颅基板是通过几个信号分子家族的整合作用以及随后转录因子复杂网络的激活而特化的。在这里,我们描述了一种细胞外基质蛋白——无嗅觉蛋白-1(Anos1)在非洲爪蟾神经嵴和颅基板发育过程中的表达和功能。Anos1被鉴定为Pax3和Zic1的靶标,这两个转录因子对于产生神经嵴和颅基板是必需且充分的。Anos1在神经胚早期的颅神经嵴祖细胞中表达,并在发育后期的颅基板衍生物中表达。我们表明,非洲爪蟾的神经嵴和感觉器官发育需要Anos1发挥功能,这与携带ANOS1突变的卡尔曼综合征患者中观察到的缺陷一致。这些发现表明anos1在颅面结构发育中具有保守功能,并表明缺乏anos1的非洲爪蟾胚胎是分析卡尔曼综合征发病机制的有用模型。