Transient Primary Cilia Mediate Robust Hedgehog Pathway-Dependent Cell Cycle Control.
Transient Primary Cilia Mediate Robust Hedgehog Pathway-Dependent Cell Cycle Control.
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DOI：
10.1016/j.cub.2020.05.004
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发表时间：
2020-07-20
期刊：
影响因子：
--
通讯作者：
Stearns T
中科院分区：
文献类型：
--
作者：
Ho EK;Tsai AE;Stearns T
调控增殖是Hedgehog （Hh）信号在发育过程中的主要功能。Hh信号转导在通路的几个步骤中需要初级纤毛。许多细胞在细胞周期结束时才形成初级纤毛。在那些产生纤毛的增殖细胞中，纤毛是一个短暂的细胞器，在G1期组装，在有丝分裂前的某个时候拆卸。因此，对初级纤毛的需求提出了一个难题：增殖信号是如何通过细胞器传递的，而细胞器只存在于细胞周期的一部分？在这里，我们在小鼠髓母细胞瘤细胞系SMB55中研究了这个问题，SMB55需要纤毛介导的Hh通路活性来增殖。我们发现SMB55细胞及其衍生的初级小脑颗粒神经元前体（GNPs）通常在G1期后进入S期，并且SMB55细胞中纤毛的存在决定了Hh通路活性的周期。通过对多个细胞周期的实时成像，我们证明了Hh通路在前一个细胞周期的G1- s期或在做出决定的细胞周期的G1期的活性足以使细胞周期进入。我们还表明，Cyclin D1有助于在多个细胞周期中持续影响通路活性。总之，我们的研究结果表明，尽管信号细胞器本身是短暂的，Hh通路对增殖的控制是非常强大的。此外，初级纤毛的短暂性可能对发育中其他hh介导的事件有影响。
The regulation of proliferation is a primary function of Hedgehog (Hh) signaling in development. Hh signal transduction requires the primary cilium for several steps in the pathway. Many cells only build a primary cilium upon cell cycle exit, in G0. In those proliferating cells that do make a cilium, it is a transient organelle, being assembled in G1 and disassembled sometime prior to mitosis. Thus, the requirement for primary cilia presents a conundrum: how are proliferative signals conveyed through an organelle that is present for only part of the cell cycle? Here we investigate this question in a mouse medulloblastoma cell line, SMB55, that requires cilium-mediated Hh pathway activity for proliferation. We show that SMB55 cells, and the primary cerebellar granule neuron precursors (GNPs) from which they derive, are often ciliated beyond G1 into S phase, and the presence of the cilium in SMB55 cells determines the periods of Hh pathway activity. Using live imaging over multiple cell cycles, we demonstrate that Hh pathway activity in either G1-S of the previous cell cycle or G1 of the cell cycle in which the decision is made is sufficient for cell cycle entry. We also show that Cyclin D1 contributes to the persistent effects of pathway activity over multiple cell cycles. Together our results reveal that even though the signaling organelle itself is transient, Hh pathway control of proliferation is remarkably robust. Further, primary cilium transience may have implications for other Hh-mediated events in development.
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影响因子：
3.3
作者：
Lee YL;Santé J;Comerci CJ;Cyge B;Menezes LF;Li FQ;Germino GG;Moerner WE;Takemaru K;Stearns T
通讯作者：
Stearns T
影响因子：
64.8
作者：
Barkai, N;Leibler, S
通讯作者：
Leibler, S
DOI：
10.3791/990
发表时间：
2009-01-16
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Lee, Hae Young;Greene, Lloyd A;Manzini, M Chiara
通讯作者：
Manzini, M Chiara
影响因子：
16.8
作者：
通讯作者：
--
DOI：
10.1126/science.1198056
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Li M;Zhang X;Jones S;Leary RJ;Lin JC;Boca SM;Carter H;Samayoa J;Bettegowda C;Gallia GL;Jallo GI;Binder ZA;Nikolsky Y;Hartigan J;Smith DR;Gerhard DS;Fults DW;VandenBerg S;Berger MS;Marie SK;Shinjo SM;Clara C;Phillips PC;Minturn JE;Biegel JA;Judkins AR;Resnick AC;Storm PB;Curran T;He Y;Rasheed BA;Friedman HS;Keir ST;McLendon R;Northcott PA;Taylor MD;Burger PC;Riggins GJ;Karchin R;Parmigiani G;Bigner DD;Yan H;Papadopoulos N;Vogelstein B;Kinzler KW;Velculescu VE
通讯作者：
Velculescu VE