Charbonnier Enrica, Fuchs Alisa, Cheung Lily S, Chayengia Mrinal, Veikkolainen Ville, Seyfferth Janine, Shvartsman Stanislav Y, Pyrowolakis George
Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Germany; Research Training Program GRK 1104, Albert-Ludwigs-University of Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Albert-Ludwigs-University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany.
Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Germany.
Dev Biol. 2015 Apr 15;400(2):258-65. doi: 10.1016/j.ydbio.2015.02.004. Epub 2015 Feb 20.
Bone Morphogenetic Proteins (BMPs) signal by activating Smad transcription factors to control a number of decisions during animal development. In Drosophila, signaling by the BMP ligand Decapentaplegic (Dpp) involves the activity of brinker (brk) which, in most contexts, is repressed by Dpp. Brk encodes a transcription factor which represses BMP signaling output by antagonizing Smad-dependent target gene activation. Here, we study BMP-dependent gene regulation during Drosophila oogenesis by following the signal transmission from Dpp to its target broad (br), a gene with a crucial function in eggshell patterning. We identify regulatory sequences that account for expression of both brk and br, and connect these to the transcription factors of the pathway. We show that Dpp directly regulates brk transcription through Smad- and Schnurri (Shn)-dependent repression. Brk is epistatic to Dpp in br expression and activates br indirectly, through removal of a repressor, which is yet to be identified. Our work provides first cis-regulatory insights into transcriptional interpretation of BMP signaling in eggshell morphogenesis and defines a transcriptional cascade that connects Dpp to target gene regulation.
骨形态发生蛋白（BMPs）通过激活Smad转录因子发出信号，以控制动物发育过程中的许多决策。在果蝇中，BMP配体Decapentaplegic（Dpp）发出的信号涉及brinker（brk）的活性，在大多数情况下，brk会被Dpp抑制。Brk编码一种转录因子，它通过拮抗Smad依赖的靶基因激活来抑制BMP信号输出。在这里，我们通过追踪从Dpp到其靶标broad（br）的信号传递，研究果蝇卵子发生过程中BMP依赖的基因调控，br是一个在卵壳图案形成中具有关键功能的基因。我们鉴定出了负责brk和br表达的调控序列，并将它们与该信号通路的转录因子联系起来。我们表明，Dpp通过Smad和Schnurri（Shn）依赖的抑制作用直接调节brk转录。在br表达中，Brk对Dpp具有上位性，并通过去除一种尚未鉴定的阻遏物间接激活br。我们的工作首次提供了关于卵壳形态发生中BMP信号转录解读的顺式调控见解，并定义了一个将Dpp与靶基因调控联系起来的转录级联反应。
