Starz-Gaiano Michelle, Melani Mariana, Wang Xiaobo, Meinhardt Hans, Montell Denise J
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Dev Cell. 2008 May;14(5):726-38. doi: 10.1016/j.devcel.2008.03.005.
In both normal development and in a variety of pathological conditions, epithelial cells can acquire migratory and invasive properties. Border cells in the Drosophila ovary provide a genetically tractable model for elucidating the mechanisms controlling such behaviors. Here we report the identification of a mutant, apontic (apt), in which the migratory population expanded and separation from the epithelium was impeded. This phenotype resembled gain-of-function of JAK/STAT activity. Gain-of-function of APT also mimicked loss of function of STAT and its key downstream target, SLBO. APT expression was induced by STAT, which bound directly to sites in the apt gene. The data suggest that a regulatory circuit between STAT, APT, and SLBO functions to convert an initially graded signal into an all-or-nothing activation of JAK/STAT and thus to proper cell specification and migration. These findings are supported by a mathematical model, which accurately simulates wild-type and mutant phenotypes.
在正常发育以及多种病理状况下，上皮细胞都能够获得迁移和侵袭特性。果蝇卵巢中的边界细胞为阐明控制此类行为的机制提供了一个易于进行遗传学研究的模型。在此，我们报告了一个名为无桥粒（apt）的突变体的鉴定结果，在该突变体中，迁移群体扩大，且与上皮的分离受到阻碍。这种表型类似于JAK/STAT活性的功能获得。APT的功能获得也模拟了STAT及其关键下游靶点SLBO的功能丧失。APT的表达由STAT诱导，STAT直接结合到apt基因中的位点。数据表明，STAT、APT和SLBO之间的调控回路发挥作用，将最初的梯度信号转化为JAK/STAT的全或无激活，从而实现正确的细胞特化和迁移。这些发现得到了一个数学模型的支持，该模型准确地模拟了野生型和突变体表型。
