JAK/STAT autocontrol of ligand-producing cell number through apoptosis
JAK/STAT autocontrol of ligand-producing cell number through apoptosis
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DOI：
10.1242/dev.079046
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发表时间：
2013-01-01
期刊：
影响因子：
4.6
通讯作者：
Pret, Anne-Marie
中科院分区：
文献类型：
--
作者：
Borensztejn, Antoine;Boissoneau, Elisabeth;Pret, Anne-Marie
在发育过程中，特定细胞通过凋亡被消除，以确保正确数量的细胞被整合到给定的组织或结构中。细胞凋亡机制在组织发育过程中是如何在体内被选择性激活的，目前还不清楚。在果蝇的卵巢中，特化的卵泡细胞（极性细胞）在卵子形成早期过量产生，并通过细胞凋亡减少到每个卵泡末端恰好有两个细胞。PCs在卵泡成熟过程中作为组织中心，因为它们是JAK/STAT通路配体未配对（Upd）的唯一来源，其形态原活性指示不同的卵泡细胞命运。本研究表明，Upd水平的降低可延长多余PCs的存活时间，下调促凋亡因子Hid，上调抗凋亡因子Diap1，抑制caspase活性。upd介导的JAK/STAT通路激活发生在PCs本身以及相邻的末端滤泡和滤泡间茎细胞中，抑制这些细胞群中的任何一个JAK/STAT信号传导可保护PCs免于凋亡。因此，统计相关的未识别中继信号对于诱导额外PC死亡是必要的。最后，阻断PCs的凋亡通过过量的Upd信号传导导致过量相邻边界细胞的特异性。因此，我们的研究结果表明，Upd和JAK/STAT信号可以诱导多余的PC细胞凋亡，从而控制PC组织中心的大小，从而产生适当水平的Upd。这是第一个将这一高度保守的信号通路与果蝇发育性凋亡联系起来的例子。
During development, specific cells are eliminated by apoptosis to ensure that the correct number of cells is integrated in a given tissue or structure. How the apoptosis machinery is activated selectively in vivo in the context of a developing tissue is still poorly understood. In the Drosophila ovary, specialised follicle cells [polar cells (PCs)] are produced in excess during early oogenesis and reduced by apoptosis to exactly two cells per follicle extremity. PCs act as an organising centre during follicle maturation as they are the only source of the JAK/STAT pathway ligand Unpaired (Upd), the morphogen activity of which instructs distinct follicle cell fates. Here we show that reduction of Upd levels leads to prolonged survival of supernumerary PCs, downregulation of the pro-apoptotic factor Hid, upregulation of the anti-apoptotic factor Diap1 and inhibition of caspase activity. Upd-mediated activation of the JAK/STAT pathway occurs in PCs themselves, as well as in adjacent terminal follicle and interfollicular stalk cells, and inhibition of JAK/STAT signalling in any one of these cell populations protects PCs from apoptosis. Thus, a Stat-dependent unidentified relay signal is necessary for inducing supernumerary PC death. Finally, blocking apoptosis of PCs leads to specification of excess adjacent border cells via excessive Upd signalling. Our results therefore show that Upd and JAK/STAT signalling induce apoptosis of supernumerary PCs to control the size of the PC organising centre and thereby produce appropriate levels of Upd. This is the first example linking this highly conserved signalling pathway with developmental apoptosis in Drosophila.