Overexpression of ptc1 inhibits induction of Shh target genes and prevents normal patterning in the neural tube
Overexpression of ptc1 inhibits induction of Shh target genes and prevents normal patterning in the neural tube
复制标题
DOI：
10.1006/dbio.1999.9311
复制
发表时间：
1999-07-15
影响因子：
2.7
通讯作者：
Scott, MP
中科院分区：
文献类型：
--
作者：
Goodrich, LV;Jung, D;Scott, MP
Patched（Ptc）是一种人类肿瘤抑制蛋白，也是Hedgehog（Hh）蛋白的候选受体，Hh蛋白调节胚胎的生长和模式。Ptc抑制Hh靶基因如Gli1和ptc1本身的表达。Hh的局部分泌似乎通过与Ptc结合并阻止其在受体细胞中发挥作用而以特定模式诱导靶基因的转录。PTC1杂合子的人表现出一系列发育缺陷，这表明当没有足够的Ptc蛋白时，一些基因会不适当地表达。为了验证Hh和Ptc活性之间的平衡对于正常发育至关重要的想法，我们在神经管中过表达Ptc。我们发现过量的Ptc足以抑制Gli1和ptc1的表达，这表明Sonic hedgehog（Shh）不能有效地发出信号。这导致神经管的部分背侧化和广泛的神经缺陷，从胚胎致死到脑积水。(C)北京：科学出版社.
Patched (Ptc) is a human tumor suppressor protein and a candidate receptor for Hedgehog (Hh) proteins, which regulate growth and patterning in embryos. Ptc represses expression of Hh target genes such as Gli1 and ptc1 itself. Localized secretion of Hh appears to induce transcription of target genes in specific patterns by binding to Ptc and preventing it from functioning in recipient cells. People who are heterozygous for PTC1 exhibit a range of developmental defects, suggesting that some genes are inappropriately expressed when there is not enough Ptc protein. To test the idea that a balance between Hh and Ptc activities is essential for normal development, we overexpressed Ptc in the neural tube. We find that excess Ptc is sufficient to inhibit expression of Gli1 and ptc1, suggesting that Sonic hedgehog (Shh) cannot signal effectively. This leads to partial dorsalization of the neural tube and a wide: spectrum of neural defects, ranging from embryonic lethality to hydrocephaly. (C) 1999 Academic Press.