Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway

Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway
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DOI:
10.1038/35084089
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发表时间:
2001-07-12
期刊:
影响因子:
64.8
通讯作者:
Anderson, KV
Anderson, KV
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Eggenschwiler, JT;Espinoza, E;Anderson, KV

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小鼠开放脑(opb)和Sonic hedgehog(Shh)基因在神经模式中具有相反的作用:脊髓中的背侧细胞类型需要opb,腹侧细胞类型需要Shh(1-3)。在这里,我们表明,opb行为下游的嘘。Shh突变体中不存在的细胞类型,包括底板,存在于Shh opb双突变体中。Shh opb双突变体的腹侧细胞类型的组织揭示了Shh-独立的机制可以沿沿着其背-腹轴图案的神经管。我们通过基于图位的方法克隆了opb,发现它编码Rab 23,Rab 23是囊泡转运蛋白Rab家族的一员。这些数据表明,背侧信号激活Rab 23的转录,以沉默背侧神经细胞中的Shh通路。
The mouse open brain (opb) and Sonic hedgehog (Shh) genes have opposing roles in neural patterning: opb is required for dorsal cell types and Shh is required for ventral cell types in the spinal cord(1-3). Here we show that opb acts downstream of Shh. Ventral cell types that are absent in Shh mutants, including the floor plate, are present in Shh opb double mutants. The organization of ventral cell types in Shh opb double mutants reveals that Shh-independent mechanisms can pattern the neural tube along its dorsal-ventral axis. We cloned opb by a map-based approach and found that it encodes Rab23, a member of the Rab family of vesicle transport proteins. The data indicate that dorsalizing signals activate transcription of Rab23 in order to silence the Shh pathway in dorsal neural cells.