Lrp4: A novel modulator of extracellular signaling in craniofacial organogenesis.
Lrp4: A novel modulator of extracellular signaling in craniofacial organogenesis.
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DOI：
10.1002/ajmg.a.33372
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发表时间：
2010-12
影响因子：
2
通讯作者：
Sharpe, Paul T.
中科院分区：
文献类型：
--
作者：
Ohazama, Atsushi;Porntaveetus, Thantrira;Ota, Masato S.;Herz, Joachim;Sharpe, Paul T.
关键词：
The low-density lipoprotein (LDL) receptor family is a large evolutionarily conserved group of transmembrane proteins. It has been shown that LDL receptor family members can also function as direct signal transducers or modulators for a broad range of cellular signalling pathways. We have identified a novel mode of signalling pathway integration/coordination that occurs outside cells during development that involves an LDL family member. Physical interaction between an extracellular protein (Wise) that binds BMP ligands and an Lrp receptor (Lrp4) that modulates Wnt signalling, acts to link these two pathways. Mutations in either Wise or Lrp4 in mice produce multiple, but identical abnormalities in tooth development that are linked to alterations in BMP and Wnt signalling. Teeth, in common with many other organs, develop by a series of epithelial - mesenchymal interactions, orchestrated by multiple cell signalling pathways. In tooth development, Lrp4 is expressed exclusively in epithelial cells and Wise mainly in mesenchymal cells. Our hypothesis, based on the mutant phenotypes, cell signalling activity changes and biochemical interactions between Wise and Lrp4 proteins, is that Wise and Lrp4 together act as an extracellular mechanism of coordinating BMP and Wnt signalling activities in epithelial-mesenchymal cell communication during development.
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