The evolutionarily conserved Hippo signaling pathway plays an important role in organ size control by regulating cell proliferation and apoptosis.Here,we identify Lingerer(Lig)as a growth suppressor using RNAi modifyi...The evolutionarily conserved Hippo signaling pathway plays an important role in organ size control by regulating cell proliferation and apoptosis.Here,we identify Lingerer(Lig)as a growth suppressor using RNAi modifying screen in Drosophila melanogaster.Loss of lig increases organ size and upregulates bantam(ban)and the expression of the Hippo pathway target genes,while overexpression of lig results in diminished ban expression and organ size reduction.We demonstrate that Lig C-terminal exhibits dominant-negative function on growth and ban expression,and thus plays an important role in organ size control and ban regulation.In addition,we provide evidence that both Yki and Mad are essential for Lig-induced ban expression.We also show that Lig regulates the expression of the Hippo pathway target genes partially via Yorkie.Moreover,we find that Lig physically interacts with and requires Salvador to restrict cell growth.Taken together,we demonstrate that Lig functions as a critical growth suppressor to control organ size via ban and Hippo signaling.展开更多
The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology. Almost a decade ago, the discovery of the Hippo signaling pathway in Drosophila shed som...The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology. Almost a decade ago, the discovery of the Hippo signaling pathway in Drosophila shed some light on this puzzling issue. The Hippo signaling pathway is highly conserved in both invertebrates and vertebrates, and plays critical roles in animal development. It controls organ size and growth by inhibiting cell proliferation and by promoting apoptosis. Malfunction of the Hippo signaling pathway leads to cancer development and tumorigenesis. Although the core of the signaling pathway is well understood, the upstream inputs and downstream transcriptional regulation are still obscure to us. In this review, we summarize the current understanding of the mechanism and the function of the Hippo signaling pathway and compare its differences between flies and mammals. We underline the crosstalk between the Hippo signaling pathway and other signaling pathways, and the possible roles of the Hippo pathway in stem cell proliferation and self-renewal.展开更多
基金This work is supported by grants from the National Basic Research Program of China(973 Program)(2010CB912101,2012CB945001,2011CB943902)the‘Strategic Priority Research Program’of the Chinese Academy of Sciences(XDA01010406)National Natural Science Foundation of China(31171394,31371462).
文摘The evolutionarily conserved Hippo signaling pathway plays an important role in organ size control by regulating cell proliferation and apoptosis.Here,we identify Lingerer(Lig)as a growth suppressor using RNAi modifying screen in Drosophila melanogaster.Loss of lig increases organ size and upregulates bantam(ban)and the expression of the Hippo pathway target genes,while overexpression of lig results in diminished ban expression and organ size reduction.We demonstrate that Lig C-terminal exhibits dominant-negative function on growth and ban expression,and thus plays an important role in organ size control and ban regulation.In addition,we provide evidence that both Yki and Mad are essential for Lig-induced ban expression.We also show that Lig regulates the expression of the Hippo pathway target genes partially via Yorkie.Moreover,we find that Lig physically interacts with and requires Salvador to restrict cell growth.Taken together,we demonstrate that Lig functions as a critical growth suppressor to control organ size via ban and Hippo signaling.
基金supported by the grants from the National Natural Science Foundation of China(No.30971646)the National Basic Research Program of China(973 Program No. 2010CB912100)+2 种基金the National Key Basic Research and Development Program of China(No.2011CB915502)the"Strategic Priority Research Program"of the Chinese Academy of Sciences(No.XDA01010406)L.Z.is the scholar of the Hundred Talents Program of the Chinese Academy of Sciences
文摘The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology. Almost a decade ago, the discovery of the Hippo signaling pathway in Drosophila shed some light on this puzzling issue. The Hippo signaling pathway is highly conserved in both invertebrates and vertebrates, and plays critical roles in animal development. It controls organ size and growth by inhibiting cell proliferation and by promoting apoptosis. Malfunction of the Hippo signaling pathway leads to cancer development and tumorigenesis. Although the core of the signaling pathway is well understood, the upstream inputs and downstream transcriptional regulation are still obscure to us. In this review, we summarize the current understanding of the mechanism and the function of the Hippo signaling pathway and compare its differences between flies and mammals. We underline the crosstalk between the Hippo signaling pathway and other signaling pathways, and the possible roles of the Hippo pathway in stem cell proliferation and self-renewal.