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Nature:控制果蝇小肠干细胞自我更新的基因

来源:Nature 2008-08-04 09:20

专题:Nature报道

像果蝇等能够进行基因操控的动物,是研究控制干细胞功能的基因网络的理想模型。现在,Takashima等人描述了果蝇的一个新体系——果蝇的后肠(hindgut),它对于研究一般意义上的干细胞分化和控制可能会具有价值。随着小肠细胞衰老,它们会被由自我更新的小肠干细胞(ISCs)所产生的新细胞取代。在果蝇中,ISCs局限在小肠内一个狭窄区域——后肠增殖区(HPZ)。这里的自我更新由Wingless(果蝇的Wnt同源基因)和Hedgehog信号通道控制,控制方式与在哺乳动物小肠中所见到的非常相似。(生物谷Bioon.com)

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Nature 454, 651-655 (24 July 2008) | doi:10.1038/nature07156

The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh signalling

Shigeo Takashima1, Marianna Mkrtchyan1, Amelia Younossi-Hartenstein1, John R. Merriam1 & Volker Hartenstein1

  1. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA

Correspondence to: Volker Hartenstein1 Correspondence and requests for materials should be addressed to V.H. (Email: volkerh@mcdb.ucla.edu).

The intestinal tract maintains proper function by replacing aged cells with freshly produced cells that arise from a population of self-renewing intestinal stem cells (ISCs). In the mammalian intestine, ISC self renewal, amplification and differentiation take place along the crypt–villus axis, and are controlled by the Wnt and hedgehog (Hh) signalling pathways1. However, little is known about the mechanisms that specify ISCs within the developing intestinal epithelium, or about the signalling centres that help maintain them in their self-renewing stem cell state. Here we show that in adult Drosophila melanogaster, ISCs of the posterior intestine (hindgut) are confined to an anterior narrow segment, which we name the hindgut proliferation zone (HPZ). Within the HPZ, self renewal of ISCs, as well as subsequent proliferation and differentiation of ISC descendants, are controlled by locally emanating Wingless (Wg, a Drosophila Wnt homologue) and Hh signals. The anteriorly restricted expression of Wg in the HPZ acts as a niche signal that maintains cells in a slow-cycling, self-renewing mode. As cells divide and move posteriorly away from the Wg source, they enter a phase of rapid proliferation. During this phase, Hh signal is required for exiting the cell cycle and the onset of differentiation. The HPZ, with its characteristic proliferation dynamics and signalling properties, is set up during the embryonic phase and becomes active in the larva, where it generates all adult hindgut cells including ISCs. The mechanism and genetic control of cell renewal in the Drosophila HPZ exhibits a large degree of similarity with what is seen in the mammalian intestine. Our analysis of the Drosophila HPZ provides an insight into the specification and control of stem cells, highlighting the way in which the spatial pattern of signals that promote self renewal, growth and differentiation is set up within a genetically tractable model system.

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