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Science:胎儿脑部发育重要信号蛋白

来源:生物通 2009-12-11 09:35

专题:Science报道

来自贝勒医学院,霍德华休斯医学院的研究人员发现了脑生长过程中的一个信号传导新机制。研究人员采用了一种特殊的方法,在小鼠出生之后来剔除Atoh1基因,从而发现了这一基因在肿瘤生长过程中的重要作用。

研究显示,在子宫中对胎儿脑部健康发育所必需的一种信号蛋白同时也在一种生长迅速的脑癌的形成中扮演了一种角色。  人们已知Atoh1转录因子在小脑的发育中扮演着其至关重要的角色。  它还与脑部的某些其它的癌症有牵连,其中包括髓母细胞瘤这种神经系统中最常见的儿科肿瘤。  然而人们对该蛋白质在胎儿出生之后的确切的功能仍然不清楚,其部分原因是因为标准的“剔除”基因的方法将会妨碍小鼠正常发育并活到出生的时候。

研究人员采用了一种逆转录病毒载体方法,在小鼠出生之后来剔除Atoh1基因。结果发现,Atoh1会调节Gli2基因的表达,因而也会影响到所谓的“Sonic  Hedgehog”信号通路。  该信号通路在正常情况下会使小脑的前体细胞保持在未分化的状态,因此它在细胞的分化与增生之间保持着微妙的平衡,这种平衡一旦出错就会导致肿瘤的生长。(生物谷Bioon.com)

生物谷推荐原始出处:

Science 4 December 2009:DOI: 10.1126/science.1181453

Deletion of Atoh1 Disrupts Sonic Hedgehog Signaling in the Developing Cerebellum and Prevents Medulloblastoma

Adriano Flora,1 Tiemo J. Klisch,1,2 Gabriele Schuster,1 Huda Y. Zoghbi1,2,3,4,*

Granule neuron precursors (GNPs) are the most actively proliferating cells in the postnatal nervous system, and mutations in pathways that control the GNP cell cycle can result in medulloblastoma. The transcription factor Atoh1 has been suspected to contribute to GNP proliferation, but its role in normal and neoplastic postnatal cerebellar development remains unexplored. We show that Atoh1 regulates the signal transduction pathway of Sonic Hedgehog, an extracellular factor that is essential for GNP proliferation, and demonstrate that deletion of Atoh1 prevents cerebellar neoplasia in a mouse model of medulloblastoma. Our data shed light on the function of Atoh1 in postnatal cerebellar development and identify a new mechanism that can be targeted to regulate medulloblastoma formation.

1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
2 Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
3 Departments of Neuroscience and Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
4 Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.

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