Dual function of suppressor of fused in Hh pathway activation and mouse spinal cord patterning
Dual function of suppressor of fused in Hh pathway activation and mouse spinal cord patterning
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DOI：
10.1016/j.ydbio.2011.11.022
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发表时间：
2012-02-15
影响因子：
2.7
通讯作者：
Liu, Aimin
中科院分区：
文献类型：
--
作者：
Liu, Jinling;Heydeck, Westley;Liu, Aimin
形态原Sonic hedgehog是Hedgehog（Hh）家族分泌蛋白中的一员，通过激活胶质瘤相关癌基因（Gli）家族转录因子，在哺乳动物脊髓沿着背腹（D/V）轴的形成中起关键作用。Suppressor of Fused（Sufu）是一种与Gli相互作用的蛋白质，通过拮抗Hh信号调节脊髓的D/V模式。腐乳在Hh通路激活和脊髓D/V模式中的功能的分子机制仍然存在争议，特别是鉴于最近的研究结果，腐乳保护Gli 2和Gli 3蛋白免受蛋白酶体降解。在目前的研究中，我们表明，Hh通路的激活和背侧扩张腹侧脊髓细胞类型的豆腐依赖于所有三个Gli家族蛋白的激活剂活性。我们还表明，腐乳在Hh信号的最大激活中起着积极的作用，Hh信号定义了哺乳动物脊髓中最腹侧的细胞命运，可能是通过保护Gli 2和Gli 3蛋白免于降解。最后，通过改变Gli激活剂活性降低的背景下Gli 3阻遏物的水平，我们揭示了Gli 3阻遏物活性对Hh通路激活和脊髓D/V模式的重要贡献。(C)2011 Elsevier Inc. All rights reserved.
The morphogen Sonic hedgehog, one of the Hedgehog (Hh) family of secreted proteins, plays a key role in patterning the mammalian spinal cord along its dorsoventral (D/V) axis through the activation of Glioma-associated oncogene (Gli) family of transcription factors. Suppressor of Fused (Sufu), a Gli-interacting protein, modulates the D/V patterning of the spinal cord by antagonizing Hh signaling. The molecular mechanisms underlying the function of Sufu in Hh pathway activation and spinal cord D/V patterning remain controversial, particularly in light of recent findings that Sufu protects Gli2 and Gli3 proteins from proteasomal degradation. In the current study, we show that Hh pathway activation and dorsal expansion of ventral spinal cord cell types in the absence of Sufu depend on the activator activities of all three Gli family proteins. We also show that Sufu plays a positive role in the maximal activation of Hh signaling that defines the ventral-most cell fate in the mammalian spinal cord, likely through protecting Gli2 and Gli3 proteins from degradation. Finally, by altering the level of Gli3 repressor on a background of reduced Gli activator activities, we reveal an important contribution of Gli3 repressor activity to the Hh pathway activation and the D/V patterning of the spinal cord. (C) 2011 Elsevier Inc. All rights reserved.