Small Chiyedza, Ramroop Johnny, Otazo Maria, Huang Lawrence H, Saleque Shireen, Govind Shubha
Biology Department, The City College of the City University of New York, New York 10031 The Graduate Center of the City University of New York, New York 10016.
Biology Department, The City College of the City University of New York, New York 10031.
Genetics. 2014 Jun;197(2):471-83. doi: 10.1534/genetics.113.159210. Epub 2013 Dec 6.
A fundamental question in hematopoietic development is how multipotent progenitors achieve precise identities, while the progenitors themselves maintain quiescence. In Drosophila melanogaster larvae, multipotent hematopoietic progenitors support the production of three lineages, exhibit quiescence in response to cues from a niche, and from their differentiated progeny. Infection by parasitic wasps alters the course of hematopoiesis. Here we address the role of Notch (N) signaling in lamellocyte differentiation in response to wasp infection. We show that Notch activity is moderately high and ubiquitous in all cells of the lymph gland lobes, with crystal cells exhibiting the highest levels. Wasp infection reduces Notch activity, which results in fewer crystal cells and more lamellocytes. Robust lamellocyte differentiation is induced even in N mutants. Using RNA interference knockdown of N, Serrate, and neuralized (neur), and twin clone analysis of a N null allele, we show that all three genes inhibit lamellocyte differentiation. However, unlike its cell-autonomous function in crystal cell development, Notch's inhibitory influence on lamellocyte differentiation is not cell autonomous. High levels of reactive oxygen species in the lymph gland lobes, but not in the niche, accompany N(RNAi)-induced lamellocyte differentiation and lobe dispersal. Our results define a novel dual role for Notch signaling in maintaining competence for basal hematopoiesis: while crystal cell development is encouraged, lamellocytic fate remains repressed. Repression of Notch signaling in fly hematopoiesis is important for host defense against natural parasitic wasp infections. These findings can serve as a model to understand how reactive oxygen species and Notch signals are integrated and interpreted in vivo.
造血发育中的一个基本问题是多能祖细胞如何获得精确的身份，同时祖细胞自身保持静止状态。在黑腹果蝇幼虫中，多能造血祖细胞支持三种细胞系的产生，对来自小生境及其分化后代的信号作出反应而进入静止状态。寄生蜂感染会改变造血过程。在这里，我们探讨Notch（N）信号在响应黄蜂感染时对片层细胞分化的作用。我们发现Notch活性在淋巴腺叶的所有细胞中适度且普遍较高，晶体细胞中的水平最高。黄蜂感染会降低Notch活性，导致晶体细胞减少而片层细胞增多。即使在N突变体中也能诱导出强大的片层细胞分化。通过RNA干扰敲低N、锯齿蛋白（Serrate）和神经化蛋白（neuralized，neur），以及对N无效等位基因进行双克隆分析，我们发现这三个基因都抑制片层细胞分化。然而，与它在晶体细胞发育中的细胞自主功能不同，Notch对片层细胞分化的抑制作用不是细胞自主的。淋巴腺叶中而非小生境中有高水平的活性氧伴随着N（RNAi）诱导的片层细胞分化和叶分散。我们的结果确定了Notch信号在维持基础造血能力方面的一种新的双重作用：在促进晶体细胞发育的同时，抑制片层细胞命运。果蝇造血过程中Notch信号的抑制对于宿主抵御自然寄生蜂感染很重要。这些发现可作为一个模型，用于理解活性氧和Notch信号在体内是如何整合和解读的。
