Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing imaginal discs
Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing imaginal discs
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DOI：
10.1016/s0925-4773(98)00130-0
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发表时间：
1998-11-01
影响因子：
2.6
通讯作者：
Busson, D
中科院分区：
文献类型：
--
作者：
Alves, G;Limbourg-Bouchon, B;Busson, D
融合 (Fu) 丝氨酸-苏氨酸激酶和融合 (Su(fu)) 产物的抑制子是胚胎和成虫盘中 Hedgehog (Hh) 信号通路的重要组成部分。在翼成虫盘中，Hh 信号诱导肘节中断 (Ci) 积累，并激活沿前/后 (A/P) 边界的修补 (ptc) 和十肢麻痹 (dpp) 表达。在本文中，我们通过使用不同类别的 fu 等位基因和无定形 Su(fu) 突变，研究了 Fu 和 Su(fu) 蛋白在翼成虫盘 Hh 靶基因表达调节中的作用。我们发现，在 A/P 边界，Fu 激酶活性参与维持高前表达和诱导晚期前部 engrailed (en) 表达。这些综合效应可以解释 Ci 积累的调节和 Dpp 形态发生素条纹的精确定位。相反，在更多不接收 Hh 信号的前部细胞中，我们发现 Fu 在 Ci 积累的调节中发挥独立于其激酶功能的作用。在这些细胞中，Fu 可能参与大蛋白质复合物的稳定，该复合物可能负责调节 Ci 裂解和/或靶向细胞核。我们认为 Fused 函数对于全长 Ci 的激活是必要的，并抵消 Su(fu) 对通路的负面影响，从而导致 en、ptc 和 dpp 表达。 (C) 1998 Elsevier Science Ireland Ltd. 保留所有权利。
The Fused (Fu) serine-threonine kinase and the Suppressor of fused (Su(fu)) product are parr of the Hedgehog (Hh) signalling pathway both in embryos and in imaginal discs. In wing imaginal discs, the Hh signal induces Cubitus interruptus (Ci) accumulation and activates patched (ptc) and decapentaplegic (dpp) expression along the anterior/posterior (A/P) boundary. In this paper, we have examined the role of the Fu and Su(fu) proteins in the regulation of Hh target gene expression in wing imaginal discs, by using different classes of fu alleles and an amorphic Su(fu) mutation. We show that, at the A/P boundary, Fu kinase activity is involved in the maintenance of high pre expression and in the induction of late anterior engrailed (en) expression. These combined effects can account for the modulation of Ci accumulation and for the precise localization of the Dpp morphogen stripe. In contrast, in more anterior cells which do not receive Hh signal, we show that Fu plays a role independent of its kinase function in the regulation of Ci accumulation. In these cells, Fu may be involved in the stabilization of a large protein complex which is probably responsible for the regulation of Ci cleavage and/or targeting to nucleus. We propose that the Fused function is necessary for the activation of full-length Ci and counteracts the negative Su(fu) effect on the pathway, leading to en, ptc and dpp expression. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.