背景回顾：Regulation of the homeodomain transcription factor WUSCHEL concentration is critical for stem cell homeostasis in Arabidopsis shoot apical meristems. 

研究基础：WUSCHEL regulates the transcription of CLAVATA3 through a concentration-dependent activation-repression switch. CLAVATA3, a secreted peptide, activates receptor kinase signaling to repress WUSCHEL transcription. Considering the revised regulation, CLAVATA3 mediated repression of WUSCHEL transcription alone will lead to an unstable system. 

结果1-CLV3-WUS：Here we show that CLAVATA3 signaling regulates nuclear-cytoplasmic partitioning of WUSCHEL to control nuclear levels and its diffusion into adjacent cells. 

结果2-WUS-EXPORTINS：Our work also reveals that WUSCHEL directly interacts with EXPORTINS via EAR-like domain which is also required for destabilizing WUSCHEL in the cytoplasm. 

结果3-CLV3对WUS转录与翻译后的双重调控：We develop a combined experimental and computational modeling approach that integrates CLAVATA3-mediated transcriptional repression of WUSCHEL and post-translational control of nuclear levels with the WUSCHEL concentration-dependent regulation of CLAVATA3. 

结论：We show that the dual control by the same signal forms a seamless connection between de novo WUSCHEL synthesis and sub-cellular partitioning in providing robustness to the WUSCHEL gradient.

 摘 要 

同源异型转录因子WUSCHEL浓度的调控对于拟南芥茎尖分生组织中的干细胞内稳态至关重要。WUSCHEL能够通过一个浓度依赖的激活-抑制开关来调控CLAVATA3基因的转录。CLAVATA3是一个分泌的多肽，能够激活受体激酶信号转导，从而抑制WUSCHEL的转录。考虑到修改后的调控，仅保留CLAVATA3介导的WUSCHEL转录抑制将会导致整个系统的不稳定性。本文中，作者发现CLAVATA3信号调控WUSCHEL的核质分配，从而控制其在细胞核中的水平，以及向邻接细胞的扩散。本文的工作还发现WUSCHEL通过EAR-like结构域，能够直接与EXPORTINS互作，同时该结构域对于胞质中WUSCHEL的不稳定化也是必需的。作者开发了一套结合实验和计算建模的方法，整合CLAVATA3介导的WUSCHEL转录抑制以及核水平的翻译后控制与WUSCHEL浓度依赖性的CLAVATA3调控。作者发现同一信号的双重调控形成了一个从头WUSCHEL合成与亚细胞分配之间的无缝连接，从而造就了一个十分稳健的WUSCHEL梯度。