Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein
Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein
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DOI：
10.1242/dev.121798
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发表时间：
2015-07-01
期刊：
影响因子：
4.6
通讯作者：
Schulz, Robert A.
中科院分区：
文献类型：
--
作者：
Tokusumi, Tsuyoshi;Tokusumi, Yumiko;Schulz, Robert A.
大理石袋(Bam of Marble，Bam)在果蝇造血过程中对淋巴腺血细胞形成器官中造血祖细胞的维持起着积极的调节作用。在这里，我们展示了Bam在淋巴腺后信号中心(PSC)细胞中的关键功能，这个细胞域被证明具有造血利基的功能。BAM在PSC细胞中表达，基因功能缺失导致PSC过度生长和解体，表明BAM在控制生态位的正常发育中起着至关重要的作用。以往的研究表明，胰岛素受体(INR)信号通路对于PSC细胞的正常增殖是必不可少的。我们分析了bam和INR通路基因双突变的淋巴腺中PSC细胞的数量，观察到bam与通路成员在基因上相互作用形成正常的PSC。ElF4A蛋白是INR信号通路下游的一个翻译因子，这一关键调控因子的功能被敲除后挽救了bam PSC的过度生长表型，进一步支持了Bam与INR通路成员的合作功能。此外，我们还发现视网膜母细胞瘤家族蛋白(RBF)，一种已被证实的细胞增殖调节蛋白，存在于PSC的细胞中，其表达依赖于bam功能。相反，干扰Decapentaplectic或Wingless信号未能影响RBF生态位细胞的表达。综上所述，这些发现表明，INR途径-Bam-RBF功能相互作用代表了一种新发现的调节PSC造血位的正确大小和组织的手段。
Bag of Marbles (Bam) is known to function as a positive regulator of hematopoietic progenitor maintenance in the lymph gland blood cell-forming organ during Drosophila hematopoiesis. Here, we demonstrate a key function for Bam in cells of the lymph gland posterior signaling center (PSC), a cellular domain proven to function as a hematopoietic niche. Bam is expressed in PSC cells, and gene loss-of-function results in PSC overgrowth and disorganization, indicating that Bam plays a crucial role in controlling the proper development of the niche. It was previously shown that Insulin receptor (InR) pathway signaling is essential for proper PSC cell proliferation. We analyzed PSC cell number in lymph glands double-mutant for bam and InR pathway genes, and observed that bam genetically interacts with pathway members in the formation of a normal PSC. The elF4A protein is a translation factor downstreamof InR pathway signaling, and functional knockdown of this crucial regulator rescued the bam PSC overgrowth phenotype, further supporting the cooperative function of Bam with InR pathway members. Additionally, we documented that the Retinoblastoma-family protein (Rbf), a proven regulator of cell proliferation, was present in cells of the PSC, with a bam function-dependent expression. By contrast, perturbation of Decapentaplegic or Wingless signaling failed to affect Rbf niche cell expression. Together, these findings indicate that InR pathway-Bam-Rbf functional interactions represent a newly identified means to regulate the correct size and organization of the PSC hematopoietic niche.