Notch signaling is essential for vascular morphogenesis in mice.
Notch signaling is essential for vascular morphogenesis in mice.
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DOI：
10.1101/gad.14.11.1343
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发表时间：
2000-06
影响因子：
10.5
通讯作者：
L. Krebs;Yingzi Xue;C. Norton;J. Shutter;M. Maguire;J. Sundberg;D. Gallahan;V. Closson;J. Kit
中科院分区：
文献类型：
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作者：
L. Krebs;Yingzi Xue;C. Norton;J. Shutter;M. Maguire;J. Sundberg;D. Gallahan;V. Closson;J. Kit
Notch基因家族编码大的跨膜受体，其是进化上保守的细胞间信号传导机制的组分。为了评估Notch 4基因的作用，我们通过基因靶向产生Notch 4缺陷小鼠。这种突变的纯合子胚胎发育正常，纯合子突变体成人是可行的和可育的。然而，Notch 4突变显示与相关Notch 1基因的靶向突变的遗传相互作用。Notch 4和Notch 1基因突变的纯合胚胎通常比Notch 1纯合突变胚胎表现出更严重的表型。Notch 1突变体和Notch 1/Notch 4双突变体胚胎在血管生成性血管重塑中均表现出严重缺陷。对编码Notch家族受体配体的基因的表达模式的分析表明，只有Dll 4基因以与早期胚胎血管系统中编码Notch 1和Notch 4受体配体的基因所预期的模式一致的模式表达。这些结果揭示了Notch信号通路在调节胚胎血管形态发生和重塑中的重要作用，并表明Notch 4基因在胚胎发育过程中不是必需的，而Notch 4和Notch 1基因在小鼠胚胎发生过程中具有部分重叠的作用。
The Notch gene family encodes large transmembrane receptors that are components of an evolutionarily conserved intercellular signaling mechanism. To assess the role of the Notch4 gene, we generated Notch4-deficient mice by gene targeting. Embryos homozygous for this mutation developed normally, and homozygous mutant adults were viable and fertile. However, the Notch4 mutation displayed genetic interactions with a targeted mutation of the related Notch1 gene. Embryos homozygous for mutations of both the Notch4 and Notch1 genes often displayed a more severe phenotype than Notch1 homozygous mutant embryos. Both Notch1 mutant and Notch1/Notch4 double mutant embryos displayed severe defects in angiogenic vascular remodeling. Analysis of the expression patterns of genes encoding ligands for Notch family receptors indicated that only the Dll4 gene is expressed in a pattern consistent with that expected for a gene encoding a ligand for the Notch1 and Notch4 receptors in the early embryonic vasculature. These results reveal an essential role for the Notch signaling pathway in regulating embryonic vascular morphogenesis and remodeling, and indicate that whereas the Notch4 gene is not essential during embryonic development, the Notch4 and Notch1 genes have partially overlapping roles during embryogenesis in mice.