dSno facilitates Baboon signaling in the Drosophila brain by switching the affinity of Medea away from Mad and toward dSmad2
dSno facilitates Baboon signaling in the Drosophila brain by switching the affinity of Medea away from Mad and toward dSmad2
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DOI：
10.1534/genetics.106.064956
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发表时间：
2006-11-01
期刊：
影响因子：
3.3
通讯作者：
Newfeld, Stuart J.
中科院分区：
文献类型：
--
作者：
Takaesu, Norma T.;Hyman-Walsh, Cathy;Newfeld, Stuart J.
对 Dpp 成体表型修饰因子的筛选导致了果蝇 Sno 癌基因 (dSno) 同源物的鉴定。 dSno 基因座很大，转录复杂，并且包含最近的逆转录转座子插入，这可能对 dSno 功能至关重要，从发育进化的角度来看，这是一个有趣的可能性。 dSno 在胚胎中枢神经系统中高度转录，并且转录物在三龄幼虫中最为丰富。 dSno 突变体幼虫的大脑视叶具有增殖缺陷，与狒狒（激活素 I 型受体）和 dSniad2 突变体中的增殖缺陷非常相似。这表明 dSno 是狒狒信号传导的中介者。 dSno 与 Medea 结合，Medea/dSno 复合物增强了对 dSmad2 的亲和力。或者，Medea/dSno 复合物对 Mad 的亲和力降低，因此，在 dSno 存在的情况下，Dpp 信号传导被拮抗。我们认为 dSno 在视叶发育中充当开关，将 Medea 从 Dpp 途径分流到激活素途径，以确保适当的增殖。靶细胞中的通路转换是一种先前未报道的调节 TGF β 信号传导的机制，也是 Sno/Ski 家族蛋白的新功能。
A screen for modifiers of Dpp adult phenotypes led to the identification of the Drosophila homolog of the Sno oncogene (dSno). The dSno locus is large, transcriptionally complex and contains a recent retrotransposon insertion that may be essential for dSno function, an intriguing possibility from the perspective of developmental evolution. dSno is highly transcribed in the embryonic central nervous system and transcripts are most abundant in third instar larvae. dSno mutant larvae have proliferation defects in the optic lobe of the brain very similar to those seen in baboon (Activin type I receptor) and dSniad2 mutants. This suggests that dSno is a mediator of Baboon signaling. dSno binds to Medea and Medea/dSno complexes have enhanced affinity for dSmad2. Alternatively, Medea/dSno complexes have reduced affinity for Mad such that, in the presence of dSno, Dpp signaling is antagonized. We propose that dSno functions as a switch in optic lobe development, shunting Medea from the Dpp pathway to the Activin pathway to ensure proper proliferation. Pathway switching in target cells is a previously unreported mechanism for regulating TGF beta signaling and a novel function for Sno/Ski family proteins.