Institute of Molecular Biology, University of Oregon, Eugene, OR, 97403, USA.
Department of Biology, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD, 21218-2685, USA.
Dev Biol. 2021 Mar;471:89-96. doi: 10.1016/j.ydbio.2020.12.008. Epub 2020 Dec 14.
Diversification of neuronal subtypes often requires stochastic gene regulatory mechanisms. How stochastically expressed transcription factors interact with other regulators in gene networks to specify cell fates is poorly understood. The random mosaic of color-detecting R7 photoreceptor subtypes in Drosophila is controlled by the stochastic on/off expression of the transcription factor Spineless (Ss). In Ss R7s, Ss induces expression of Rhodopsin 4 (Rh4), whereas in Ss R7s, the absence of Ss allows expression of Rhodopsin 3 (Rh3). Here, we find that the transcription factor Runt, which is initially expressed in all R7s, is sufficient to promote stochastic Ss expression. Later, as R7s develop, Ss negatively feeds back onto Runt to prevent repression of Rh4 and ensure proper fate specification. Together, stereotyped and stochastic regulatory inputs are integrated into feedforward and feedback mechanisms to control cell fate.
神经元亚型的多样化通常需要随机的基因调控机制。然而，人们对于随机表达的转录因子如何与基因网络中的其他调控因子相互作用以特化细胞命运知之甚少。果蝇中颜色探测 R7 光感受器亚型的随机镶嵌是由转录因子 Spinoseless（Ss）的随机开启/关闭表达所控制的。在 Ss R7 中，Ss 诱导 Rhodopsin 4（Rh4）的表达，而在 Ss R7 中，Ss 的缺失允许 Rhodopsin 3（Rh3）的表达。在这里，我们发现最初在所有 R7 中表达的转录因子 Runt 足以促进随机的 Ss 表达。后来，随着 R7 的发育，Ss 会对 Runt 产生负反馈，以防止 Rh4 的抑制并确保正确的命运特化。综上所述，定型和随机的调控输入被整合到前馈和反馈机制中，以控制细胞命运。
