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扇形蛋白是河马肿瘤抑制通路的成员,通过对神经母细胞增殖的非经典调控来控制果蝇大脑中蘑菇体的大小。

Scalloped a member of the Hippo tumor suppressor pathway controls mushroom body size in Drosophila brain by non-canonical regulation of neuroblast proliferation.

作者信息

Rohith Basavanahalli Nanjundaiah, Shyamala Baragur Venkatanarayanasetty

机构信息

Developmental Genetics Laboratory, Department of Studies in Zoology, University of Mysore, Mysuru 570006, India.

Developmental Genetics Laboratory, Department of Studies in Zoology, University of Mysore, Mysuru 570006, India.

出版信息

Dev Biol. 2017 Dec 15;432(2):203-214. doi: 10.1016/j.ydbio.2017.10.016.

DOI:10.1016/j.ydbio.2017.10.016
PMID:29080790
Abstract

Cell proliferation, growth and survival are three different basic processes which converge at determining a fundamental property -the size of an organism. Scalloped (Sd) is the first characterised transcriptional partner to Yorkie (Yki), the downstream effector of the Hippo pathway which is a highly potential and evolutionarily conserved regulator of organ size. Here we have studied the hypomorphic effect of sd on the development of Mushroom Bodies (MBs) in Drosophila brain. We show that, sd non-function results in an increase in the size of MBs. We demonstrate that, sd regulation on MB size operates through multiple routes. Sd expressed in the differentiated MB neurons, imposes non-cell autonomous repression on the proliferation of MB precursor cells, and Sd expression in the MB neuroblasts (NB) cell autonomously represses mushroom body neuroblast (MBNB) proliferation. Further Sd in Kenyon cells (KCs) imparts a cell autonomous restriction on their growth. Our findings are distinctive because, while the classical sd loss of function phenotypes in eye, wing and lymph gland are reported as loss of tissue or reduced organ size, the present study shows that, Sd inactivation in the developing MB, promotes precursor cell proliferation and results in an increase in the organ size.

摘要

细胞增殖、生长和存活是三个不同的基本过程,它们共同决定了一个基本特性——生物体的大小。扇贝蛋白(Sd)是第一个被鉴定出的与约克蛋白(Yki)相互作用的转录伙伴,Yki是Hippo信号通路的下游效应因子,该信号通路是器官大小的一个极具潜力且在进化上保守的调节因子。在这里,我们研究了sd基因功能减弱对果蝇大脑中蘑菇体(MBs)发育的影响。我们发现,sd基因功能缺失会导致蘑菇体尺寸增大。我们证明,sd基因对蘑菇体大小的调节是通过多种途径实现的。在分化的蘑菇体神经元中表达的Sd,对蘑菇体前体细胞的增殖施加非细胞自主性抑制作用,而在蘑菇体神经母细胞(NB)中表达的Sd则细胞自主性地抑制蘑菇体神经母细胞(MBNB)的增殖。此外,肯扬细胞(KCs)中的Sd对其生长施加细胞自主性限制。我们的研究结果具有独特性,因为虽然在眼睛、翅膀和淋巴腺中经典的sd基因功能缺失表型被报道为组织缺失或器官尺寸减小,但本研究表明,在发育中的蘑菇体中Sd失活会促进前体细胞增殖并导致器官尺寸增大。

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1
Scalloped a member of the Hippo tumor suppressor pathway controls mushroom body size in Drosophila brain by non-canonical regulation of neuroblast proliferation.扇形蛋白是河马肿瘤抑制通路的成员,通过对神经母细胞增殖的非经典调控来控制果蝇大脑中蘑菇体的大小。
Dev Biol. 2017 Dec 15;432(2):203-214. doi: 10.1016/j.ydbio.2017.10.016.
2
SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila.扇贝状蛋白与YORKIE相互作用,YORKIE是果蝇中河马肿瘤抑制途径的核效应因子。
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Opposing transcriptional and post-transcriptional roles for Scalloped in binary Hippo-dependent neural fate decisions.Scalloped 在二元 Hippo 依赖的神经命运决定中发挥转录和转录后作用。
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The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control.转录因子扇贝(Scalloped)所属的TEAD/TEF家族在器官大小控制中介导Hippo信号通路。
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Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling.果蝇细胞极性调节因子Scribbled的缺失通过受损的Hippo信号通路促进上皮组织过度生长并与致癌性Ras-Raf协同作用。
BMC Dev Biol. 2011 Sep 29;11:57. doi: 10.1186/1471-213X-11-57.

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