Signals transduced by Ca2+/calcineurin and NFATc3/c4 pattern the developing vasculature
Signals transduced by Ca2+/calcineurin and NFATc3/c4 pattern the developing vasculature
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DOI：
10.1016/s0092-8674(01)00396-8
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发表时间：
2001-06-29
期刊：
影响因子：
64.5
通讯作者：
Crabtree, GR
中科院分区：
文献类型：
--
作者：
Graef, IA;Chen, F;Crabtree, GR
血管的发育需要生长的血管和它们的支持组织之间有序的信号交换，但是对这种通信的细胞内信号通路知之甚少。我们发现，NFATc 4和相关NFATc 3基因都被破坏的小鼠在E11左右死亡，血管组装普遍存在缺陷，血管过度和无序地生长到神经管和体节中。由于钙调神经磷酸酶被认为控制NFATc蛋白的核定位，我们将突变引入钙调神经磷酸酶基因，该基因阻止Ca 2+信号激活磷酸酶。这些CnB突变小鼠表现出与NFATc 3/c4缺失小鼠相似的血管发育异常。我们发现，钙调磷酸酶的功能是短暂的E7.5和E8.5之间。因此，早期的钙调磷酸酶/NFAT信号传导启动了血管和周围组织之间的后期串扰，从而形成脉管系统。
Vascular development requires an orderly exchange of signals between growing vessels and their supporting tissues, but little is known of the intracellular signaling pathways underlying this communication. We find that mice with disruptions of both NFATc4 and the related NFATc3 genes die around E11 with generalized defects in vessel assembly as well as excessive and disorganized growth of vessels into the neural tube and somites. Since calcineurin is thought to control nuclear localization of NFATc proteins, we introduced a mutation into the calcineurin a gene that prevents phosphatase activation by Ca2+ signals. These CnB mutant mice exhibit vascular developmental abnormalities similar to the NFATc3/c4 null mice. We show that calcineurin function is transiently required between E7.5 and E8.5. Hence, early calcineurin/NFAT signaling initiates the later cross-talk between vessels and surrounding tissues that pattern the vasculature.