A trophic role for Wnt-Ror kinase signaling during developmental pruning in Caenorhabditis elegans
A trophic role for Wnt-Ror kinase signaling during developmental pruning in Caenorhabditis elegans
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DOI：
10.1038/nn.2347
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发表时间：
2009-08-01
影响因子：
25
通讯作者：
Kubo, Takeo
中科院分区：
文献类型：
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作者：
Hayashi, Yu;Hirotsu, Takaaki;Kubo, Takeo
在发育修剪过程中，神经突被选择用于消除或并入成熟回路的分子机制仍然未知。营养理论假设，由靶细胞或周围细胞提供的局部线索抑制神经突消除。然而，没有广泛保守的因子介导的营养功能已被确定。我们发现，在秀丽隐杆线虫的特定神经突的发育存活在很大程度上取决于检测的形态Wnt的Ror激酶CAM-1，这是一个跨膜酪氨酸激酶与卷曲域。Wnt基因或cam-1突变增强了神经突的消除，而过表达cam-1则以Wnt依赖的方式抑制了神经突的消除。此外，这些基因的突变抵消了mbr-1突变的影响，mbr-1编码一种促进神经突消除的转录因子。这些结果揭示了非典型Wnt途径的营养作用，并加强了经典的发育修剪模型。
The molecular mechanism by which neurites are selected for elimination or incorporation into the mature circuit during developmental pruning remains unknown. The trophic theory postulates that local cues provided by target or surrounding cells act to inhibit neurite elimination. However, no widely conserved factor mediating this trophic function has been identified. We found that the developmental survival of specific neurites in Caenorhabditis elegans largely depends on detection of the morphogen Wnt by the Ror kinase CAM-1, which is a transmembrane tyrosine kinase with a Frizzled domain. Mutations in Wnt genes or in cam-1 enhanced neurite elimination, whereas overexpression of cam-1 inhibited neurite elimination in a Wnt-dependent manner. Moreover, mutations in these genes counteracted the effect of a mutation in mbr-1, which encodes a transcription factor that promotes neurite elimination. These results reveal the trophic role of an atypical Wnt pathway and reinforce the classical model of developmental pruning.