EGFR/MAPK Signaling Regulates the Proliferation of Drosophila Renal and Nephric Stem Cells
EGFR/MAPK Signaling Regulates the Proliferation of Drosophila Renal and Nephric Stem Cells
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DOI：
10.1016/j.jgg.2014.11.007
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发表时间：
2015-01-20
影响因子：
5.9
通讯作者：
Cai, Yu
中科院分区：
文献类型：
--
作者：
Li, Zhouhua;Liu, Sen;Cai, Yu
组织稳态，通过自我更新和分化的居民干细胞完成，是至关重要的维持成年组织在动物的一生。成年果蝇马氏管（MT或蝇肾）由肾和肾干细胞（RNSC）通过自我更新分裂维持，然而，RNSC增殖和分化是如何调节的尚不清楚。在这里，我们表明，EGFR/MAPK信号是RNSC的维持，但需要RNSC在体内增殖。EGFR/MAPK通路的失活阻断或极大地延迟RNSC细胞周期进展;相反，EGFR/MAPK信号传导的过度活化导致RNSC过度增殖并破坏肾母细胞（RB）（RNSC分裂的直接子代）的正常分化。我们的数据进一步表明，EGFR/MAPK信号传导功能独立于JAK/STAT信号传导，并且dMyc和CycE部分介导MT中的EGFR/MAPK信号传导。总之，我们的数据表明EGFR/MAPK信号在调节RNSC增殖中的主要作用，这可能为理解哺乳动物损伤后的肾脏修复和再生提供重要线索。
Tissue homeostasis, accomplished through the self-renewal and differentiation of resident stem cells, is critical for the maintenance of adult tissues throughout an animal's lifetime. Adult Drosophila Malpighian tubules (MTs or fly kidney) are maintained by renal and nephric stem cells (RNSCs) via self-renewing divisions, however, it is unclear how RNSC proliferation and differentiation are regulated. Here we show that EGFR/MAPK signaling is dispensable for RNSC maintenance, but required for RNSC proliferation in vivo. Inactivation of the EGFR/MAPK pathway blocks or greatly retards RNSC cell cycle progression; conversely, over-activation of EGFR/MAPK signaling results in RNSC over-proliferation and disrupts the normal differentiation of renablasts (RBs), the immediate daughters of RNSC divisions. Our data further suggest that EGFR/MAPK signaling functions independently of JAK/STAT signaling and that dMyc and CycE partially mediate EGFR/MAPK signaling in MTs. Together, our data suggest a principal role of EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important clues for understanding mammalian kidney repair and regeneration following injury.