Notch1 signals through jagged2 to regulate apoptosis in the apical ectodermal ridge of the developing limb bud
Notch1 signals through jagged2 to regulate apoptosis in the apical ectodermal ridge of the developing limb bud
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DOI：
10.1002/dvdy.20590
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发表时间：
2005-12-01
影响因子：
2.5
通讯作者：
Logan, MPO
中科院分区：
文献类型：
--
作者：
Francis, JC;Radtke, F;Logan, MPO
Notch受体家族参与多种发育过程，包括细胞命运指定、细胞增殖以及细胞分化和组织形态形成过程中的细胞存活决定。NOTCH1和Notch配体在发育中的肢体中表达，Notch信号与构成肢体的各种组织的形成有关，如骨骼、肌肉和血管系统。缺口信号也与调节整体肢体大小有关。我们使用Notch1的条件等位基因与两个不同的Cre转基因系结合，删除了Notch1在肢体间充质、顶端外胚脊(AER)和肢体外胚层中的功能。我们证明，Notch1和Jagged2参与的Notch信号转导是调节组成AER的Fgf8表达细胞数量所必需的，并且成纤维细胞生长因子信号转导水平的调节对于正常肢体形成过程中的手指自由是重要的。AER范围的调节是通过Notch信号正向调节AER中的细胞凋亡来实现的。我们还证明了Notch1对于肢体间充质的所有导数的正确形成不是必需的。
The Notch family of receptors is involved in a wide variety of developmental processes, including cell fate specification, cell proliferation, and cell survival decisions during cell differentiation and tissue morphogenesis. Notch1 and Notch ligands are expressed in the developing limbs, and Notch signalling has been implicated in the formation of a variety of tissues that comprise the limb, such as the skeleton, musculature, and vasculature. Notch signalling has also been implicated in regulating overall limb size. We have used a conditional allele of Notch1 in combination with two different Cre transgenic lines to delete Notch1 function either in the limb mesenchyme or in the apical ectodermal ridge (AER) and limb ectoderm. We demonstrate that Notch signalling, involving Notch1 and Jagged2, is required to regulate the number of Fgf8-expressing cells that comprise the AER and that regulation of the levels of fibroblast growth factor signalling is important for the freeing of the digits during normal limb formation. Regulation of the extent of the AER is achieved by Notch signalling positively regulating apoptosis in the AER. We also demonstrate that Notch1 is not required for proper formation of all the derivatives of the limb mesenchyme.