Guillemin K, Groppe J, Ducker K, Treisman R, Hafen E, Affolter M, Krasnow M A
Department of Biochemistry, Stanford University School of Medicine, CA 94305, USA.
Development. 1996 May;122(5):1353-62. doi: 10.1242/dev.122.5.1353.
We identified a Drosophila gene, pruned, that regulates formation of the terminal branches of the tracheal (respiratory) system. These branches arise by extension of long cytoplasmic processes from terminal tracheal cells towards oxygen-starved tissues, followed by formation of a lumen within the processes. The pruned gene is expressed in terminal cells throughout the period of terminal branching. pruned encodes the Drosophila homologue of serum response factor (SRF), which functions with an ETS domain ternary complex factor as a growth-factor-activated transcription complex in mammalian cells. In pruned loss of function mutants, terminal cells fail to extend cytoplasmic projections. A constitutively activated SRF drives formation of extra projections that grow out in an unregulated fashion. An activated ternary complex factor has a similar effect. We propose that the Drosophila SRF functions like mammalian SRF in an inducible transcription complex, and that activation of this complex by signals from target tissues induces expression of genes involved in cytoplasmic outgrowth.
我们鉴定出一个果蝇基因——“修剪”基因,它调控气管(呼吸系统)末端分支的形成。这些分支是由末端气管细胞向缺氧组织伸出长的细胞质突起,随后在突起内形成管腔而产生的。“修剪”基因在末端分支形成的整个时期都在末端细胞中表达。“修剪”基因编码血清反应因子(SRF)的果蝇同源物,在哺乳动物细胞中,血清反应因子与一个ETS结构域三元复合因子一起作为生长因子激活的转录复合体发挥作用。在“修剪”基因功能缺失突变体中,末端细胞无法伸出细胞质突起。组成型激活的SRF会驱动额外突起的形成,这些突起以不受调控的方式生长。激活的三元复合因子也有类似的作用。我们提出,果蝇SRF在诱导型转录复合体中的功能与哺乳动物SRF类似,并且来自靶组织的信号对该复合体的激活会诱导参与细胞质生长的基因的表达。