Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis
Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis
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DOI：
10.1016/s0736-5748(00)00071-x
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发表时间：
2001-02-01
影响因子：
1.8
通讯作者：
Matsuno, K
中科院分区：
文献类型：
--
作者：
Kishi, N;Tang, ZY;Matsuno, K
Notch信号通过调控细胞间通讯，在多细胞生物的细胞命运调控中起着重要作用。果蝇deltex基因编码Notch通路的一个调节剂，该调节剂已被证明与Notch的锚蛋白重复序列发生物理相互作用。我们分离了四种不同的dna，分别对应于deltex的小鼠同源物——小鼠Deltex1 （MDTX1）、小鼠Deltex2 （MDTX2）、小鼠Deltex2 DeltaE （MDTX2 DeltaE）和小鼠Deltex3 （MDTX3）。推导出的这4个cdna的氨基酸序列在长度上与果蝇Deltex及其人类同源物DTX1高度相似，尽管它们具有不同的结构特征。MDTX蛋白形成同型和异型多聚体。我们发现这些基因在中枢、周围神经系统和胸腺中表达，与小鼠Notch1的基因重叠。在哺乳动物组织培养细胞中，四种小鼠deltex同源物中的任何一种的过表达都会抑制E47的转录活性，E47是一种基本的螺旋-环-螺旋（bHLH）蛋白，其抑制方式类似于人类Notch1或DTX1的激活形式。此外，在分化诱导条件下，C2C12细胞中MDTX2和MDTX2 DeltaE的过表达抑制了肌生成素（myogenin）的表达，肌生成素是肌生成的转录因子之一；这也类似于先前报道的组成型激活Notch的活性。此外，任何MDTX基因在爪蟾胚胎中的错误表达都会导致神经细胞粘附分子（N-CAM）基因表达区域的扩增，N-CAM基因是神经上皮的标志。总之，我们的研究结果表明，这些小鼠deltex同源物参与了脊椎动物Notch信号传导和神经发生的调节。(c) 2001年数据。Elsevier Science Ltd.出版。版权所有。
Notch signaling plays an important role in cell-fate specification in multicellular organisms by regulating cell-cell communication. The Drosophila deltex gene encodes a modulator of the Notch pathway that has been shown to interact physically with the Ankyrin repeats of Notch. We isolated four distinct cDNAs corresponding to mouse homologs of deltex - mouse Deltex1 (MDTX1), mouse Deltex2 (MDTX2), mouse Deltex2 DeltaE (MDTX2 DeltaE), and mouse Deltex3 (MDTX3). Deduced amino acid sequences of these four cDNAs showed a high degree of similarity to Drosophila Deltex and its human homolog, DTX1 throughout their lengths, even though they possess distinct structural features. MDTX proteins formed homotypic and heterotypic multimers. We found that these genes were expressed in the central, peripheral nervous system and in the thymus, overlapping with those of mouse Notch1. In mammalian tissue culture cells, overexpression of any of the four mouse deltex homologs suppressed the transcriptional activity of E47, a basic helix-loop-helix (bHLH) protein: in a manner similar to suppression by an activated form of human Notch1 or human DTX1. In addition, overexpression of MDTX2 and MDTX2 DeltaE in C2C12 cells under differentiation-inducing conditions suppressed the expression of myogenin, one of the myogenic transcriptional factors; this was also similar to a previously reported activity of constitutively activated Notch. Furthermore, misexpression of any of the MDTX genes in Xenopus embryos resulted in an expansion of the region expressing the neural cell adhesion molecule (N-CAM) gene, a marker for the neuroepithelium. Collectively, our results suggest that these mouse deltex homologs are involved in vertebrate Notch signaling and regulation of neurogenesis. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved.