Notch pathway regulation of neural crest cell development in vivo.

Notch pathway regulation of neural crest cell development in vivo.
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DOI:
10.1002/dvdy.23717
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发表时间:
2012-02
影响因子:
2.5
通讯作者:
Yutzey, Katherine E.
Yutzey, Katherine E.
中科院分区:
生物学3区
文献类型:
--
作者:
Mead, Timothy J.;Yutzey, Katherine E.

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检查了Notch信号在体内小鼠神经嵴衍生细胞谱系中的功能。体内神经嵴细胞 (NCC) 中 Notch 信号条件性获得 (Wnt1Cre;RosaNotch) 或损失 (Wnt1Cre;RBP-Jf/f) 会导致颅面、心脏和躯干异常。 Wnt1Cre;RosaNotch 胚胎中存在明显的严重颅面畸形,而 Wnt1Cre;RBP-Jf/f 小鼠中则存在较不严重的颅骨异常。当 NCC 中 Notch 信号传导增加或减少时,心脏神经嵴迁移缺陷会导致心脏流出道畸形。 Wnt1Cre;RosaNotch 和 Wnt1Cre;RBP-Jf/f 胚胎中的咽部 NCC 衍生物的平滑肌细胞分化也受到损害。 Wnt1Cre;RosaNotch 胚胎的背根神经节中神经发生缺失,胶质细胞生成增加,而 Wnt1Cre;RBP-Jf/f 胚胎中神经发生增加,胶质细胞生成减少。总之,这些研究表明,在 NCC 迁移、增殖和分化过程中,适当水平的 Notch 信号传导具有重要的细胞自主作用,对颅面、心脏和神经源性发育和疾病具有重要影响。
The function of Notch signaling in murine neural crest-derived cell lineages in vivo was examined. Conditional gain (Wnt1Cre;RosaNotch) or loss (Wnt1Cre;RBP-Jf/f) of Notch signaling in neural crest cells (NCCs) in vivo results in craniofacial, cardiac, and trunk abnormalities. Severe craniofacial malformations are apparent in Wnt1Cre;RosaNotch embryos, while less severe skull abnormalities are evident in Wnt1Cre;RBP-Jf/f mice. Deficient cardiac neural crest migration, resulting in cardiac outflow tract malformations, occurs with increased or decreased Notch signaling in NCCs. Smooth muscle cell differentiation also is impaired in pharyngeal NCC derivatives in both Wnt1Cre;RosaNotch and Wnt1Cre;RBP-Jf/f embryos. Neurogenesis is absent and gliogenesis is increased in the dorsal root ganglia of Wnt1Cre;RosaNotch embryos, while neurogenesis is increased and gliogenesis is decreased in Wnt1Cre;RBP-Jf/f embryos. Together, these studies demonstrate essential cell-autonomous roles for appropriate levels of Notch signaling during NCC migration, proliferation, and differentiation with critical implications in craniofacial, cardiac, and neurogenic development and disease.
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