Schlichting Karin, Demontis Fabio, Dahmann Christian
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Dev Biol. 2005 Mar 1;279(1):142-54. doi: 10.1016/j.ydbio.2004.12.008.
The subdivision of the Drosophila wing imaginal disc into anterior and posterior compartments requires a transcriptional response to Hedgehog signaling. However, the genes regulated by Hedgehog signal transduction that mediate the segregation of anterior and posterior cells have not been identified. Here, we molecularly characterize the previously predicted gene cad99C and show that it is regulated by Hedgehog signaling. Cad99C encodes a transmembrane protein with a molecular weight of approximately 184 kDa that contains 11 cadherin repeats in its extracellular domain and a conserved type I PDZ-binding site at its C-terminus. The levels of cad99C RNA and protein are low throughout the wing imaginal disc. However, in the pouch region, these levels are elevated in a strip of anterior cells along the A/P boundary where the Hedgehog signal is transduced. Ectopic expression of Hedgehog, or the Hedgehog-regulated transcription factor Cubitus interruptus, induces high-level expression of Cad99C. Conversely, blocking Hedgehog signal transduction by either inactivating Smoothened or Cubitus interruptus reduces high-level Cad99C expression. Finally, by analyzing mutant clones of cells, we show that Cad99C is not essential for cell segregation at the A/P boundary. We conclude that cad99C is a novel Hedgehog-regulated gene encoding a member of the cadherin superfamily in Drosophila.
果蝇翅成虫盘划分为前后两个区域需要对Hedgehog信号产生转录反应。然而，尚未确定由Hedgehog信号转导调控的、介导前后细胞分离的基因。在这里，我们对先前预测的基因cad99C进行了分子特征分析，并表明它受Hedgehog信号调控。Cad99C编码一种分子量约为184 kDa的跨膜蛋白，其胞外结构域含有11个钙黏蛋白重复序列，C端有一个保守的I型PDZ结合位点。在整个翅成虫盘中，cad99C的RNA和蛋白质水平都很低。然而，在翅袋区域，沿着A/P边界转导Hedgehog信号的一条前侧细胞带中，这些水平会升高。异位表达Hedgehog或受Hedgehog调控的转录因子Cubitus interruptus会诱导Cad99C的高水平表达。相反，通过使Smoothened或Cubitus interruptus失活来阻断Hedgehog信号转导会降低Cad99C的高水平表达。最后，通过分析细胞的突变克隆，我们表明Cad99C对于A/P边界处的细胞分离并非必需。我们得出结论，cad99C是一个新的受Hedgehog调控的基因，在果蝇中编码钙黏蛋白超家族的一个成员。
