Cadinouche M Z, Liversage R A, Muller W, Tsilfidis C
Eye Research Institute of Canada, Toronto Hospital, Western Division, Ontario, Canada.
Dev Dyn. 1999 Mar;214(3):259-68. doi: 10.1002/(SICI)1097-0177(199903)214:3<259::AID-AJA9>3.0.CO;2-G.
Larval and adult newts provide important experimental models to study limb development and regeneration. These animals have exceptional ability to regenerate their appendages, as well as other vital structures. Our research examines the role of the fringe gene (fng) in the developing and regenerating adult newt forelimb. Fringe codes for a secretory protein. It was first discovered in Drosophila, and later homologues were isolated in Xenopus laevis, chick and mouse. This gene has been highly conserved throughout evolution, indicating its crucial role in vertebrate and invertebrate development. We have isolated, cloned, and sequenced the full length of the Notophthalmus viridescens radical fringe cDNA (nrFng) by screening a newt forelimb blastema cDNA library with a 500-bp fragment of the Xenopus lunatic fringe cDNA. The newt fringe cDNA codes for a 396 amino acid protein with a predicted N-terminal signal sequence. Newt fringe shows high homology with radical fringe homologues of many species. Whole mount mRNA in situ hybridization on several stages of newt limb development reveals that nrFng is first expressed in the limb field, with intense expression as the limb bud develops. However, gene expression diminishes with more advanced digit development. A significant role in adult forelimb regeneration is also evident, as we isolated the cDNA from a regeneration-specific library and found it highly expressed during the regenerative phases of active cell division and then down regulated at sites undergoing differentiation and morphogenesis.
幼体和成年蝾螈为研究肢体发育和再生提供了重要的实验模型。这些动物具有非凡的肢体及其他重要结构的再生能力。我们的研究探讨了边缘基因（fng）在成年蝾螈前肢发育和再生过程中的作用。边缘基因编码一种分泌蛋白。它最初是在果蝇中发现的，后来在非洲爪蟾、鸡和小鼠中分离出了同源物。该基因在整个进化过程中高度保守，表明其在脊椎动物和无脊椎动物发育中起着关键作用。我们通过用非洲爪蟾边缘基因cDNA的一个500碱基对片段筛选蝾螈前肢芽基cDNA文库，分离、克隆并测序了绿红东美螈激进边缘基因cDNA（nrFng）的全长。蝾螈边缘基因cDNA编码一个含有预测N端信号序列的396个氨基酸的蛋白质。蝾螈边缘基因与许多物种的激进边缘基因同源物具有高度同源性。对蝾螈肢体发育几个阶段进行的全胚胎mRNA原位杂交显示，nrFng最初在肢体区域表达，随着肢芽发育表达增强。然而，随着指的进一步发育，基因表达减弱。在成年前肢再生中其重要作用也很明显，因为我们从一个再生特异性文库中分离出了该cDNA，并发现它在活跃细胞分裂的再生阶段高度表达，然后在经历分化和形态发生的部位下调。
