Fregoso Lomas Mariana, De Vito Scott, Boisclair Lachance Jean-François, Houde Josée, Nilson Laura A
Department of Biology, McGill University, 1205 Doctor Penfield Avenue, Montréal, QC H3A 1B1, Canada.
Department of Biology, McGill University, 1205 Doctor Penfield Avenue, Montréal, QC H3A 1B1, Canada.
Curr Biol. 2016 Oct 10;26(19):2572-2582. doi: 10.1016/j.cub.2016.07.073. Epub 2016 Sep 1.
A relatively small number of signaling pathways drive a wide range of developmental decisions, but how this versatility in signaling outcome is generated is not clear. In the Drosophila follicular epithelium, localized epidermal growth factor receptor (EGFR) activation induces distinct cell fates depending on its location. Posterior follicle cells respond to EGFR activity by expressing the T-box transcription factors Midline and H15, while anterior cells respond by expressing the homeodomain transcription factor Mirror. We show that the choice between these alternative outputs of EGFR signaling is regulated by antiparallel gradients of JAK/STAT and BMP pathway activity and that mutual repression between Midline/H15 and Mirror generates a bistable switch that toggles between alternative EGFR signaling outcomes. JAK/STAT and BMP pathway input is integrated through their joint and opposing regulation of both sides of this switch. By converting this positional information into a binary decision between EGFR signaling outcomes, this regulatory network ultimately allows the same ligand-receptor pair to establish both the anterior-posterior (AP) and dorsal-ventral (DV) axes of the tissue.
相对少数的信号通路驱动着广泛的发育决策，但信号输出的这种多功能性是如何产生的尚不清楚。在果蝇卵泡上皮中，局部表皮生长因子受体（EGFR）激活根据其位置诱导不同的细胞命运。后部卵泡细胞通过表达T盒转录因子中线（Midline）和H15对EGFR活性作出反应，而前部细胞则通过表达同源域转录因子镜像（Mirror）作出反应。我们表明，EGFR信号传导的这些替代输出之间的选择受JAK/STAT和BMP信号通路活性的反平行梯度调节，并且中线/H15和镜像之间的相互抑制产生了一个双稳态开关，该开关在替代的EGFR信号传导结果之间切换。JAK/STAT和BMP信号通路的输入通过它们对该开关两侧的联合和相反调节而整合。通过将这种位置信息转化为EGFR信号传导结果之间的二元决策，这个调节网络最终允许相同的配体-受体对建立组织的前后（AP）轴和背腹（DV）轴。
