Asymmetric localization of Numb in the chick somite and the influence of myogenic signals
Asymmetric localization of Numb in the chick somite and the influence of myogenic signals
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DOI：
10.1002/dvdy.20672
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发表时间：
2006-03-01
影响因子：
2.5
通讯作者：
Lassar, AB
中科院分区：
文献类型：
--
作者：
Holowacz, T;Zeng, L;Lassar, AB
虽然Notch信号在体节的形成中发挥了重要作用，但对其在体节成熟后期的作用却知之甚少。在这里，我们研究了在鸡胚胎体节成熟过程中控制Notch拮抗剂Numb表达的信号和转录因子。Numb mRNA存在于上皮性肌节中，并在形成肌节时表达增加。Numb蛋白在体节成熟过程中表现出非常特殊的亚细胞定位和动态表达。Numb蛋白不对称地分布在皮肌节背内侧唇部分裂细胞基侧的皮质新月体中，随后均匀分布于分化的肌瘤细胞中。用Wnt-3a和Shh的组合或外胚层信号和noggin处理体节，这两种方法都可以诱导肌细胞发生，但对Numb转录水平没有显著影响，但确实导致Numb蛋白水平的显著增加，Numb蛋白均匀分布在所形成的肌管的细胞质中。在体节中强制表达MyoD类似地诱导了整个细胞质中高水平的Numb蛋白，而不影响Numb的mRNA水平。我们还发现，促进躯体肌发生或强迫MyoD表达的信号诱导了Notch配体Serrate-2的表达。我们的发现表明，Notch信号在肌节中被特异性地抑制，在皮肌节背内侧唇的分裂细胞中Numb的不对称表达可能调节这些细胞是否继续分裂或分化为肌瘤细胞。
Whereas Notch signaling is known to play an essential role in the formation of somites, its role during later stages of somite maturation is less well understood. Here, we examine the signals and transcription factors that control the expression of the Notch antagonist, Numb, during somite maturation in the chick embryo. Numb mRNA is present in the epithelial somite and is increased in expression in the forming myotome. Numb protein displays a very specific subcellular localization and dynamic expression during somite maturation. Numb protein is asymmetrically localized in a cortical crescent on the basal side of dividing cells in the dorsomedial lip of the dermomyotome and is subsequently uniformly distributed throughout differentiated myotomal cells. Treatment of somites with either the combination of Wnt-3a and Shh, or ectodermal signals plus noggin, both of which induce somitic myogenesis, did not significantly affect Numb transcript levels but did lead to a dramatic increase in the levels of Numb protein, which was uniformly distributed throughout the cytoplasm of the resultant myotubes. Forced expression of MyoD in somites similarly induced high levels of Numb protein throughout the cytoplasm, without affecting Numb mRNA levels. We also found that signals that promote somitic myogenesis or forced MyoD expression induced expression of the Notch ligand, Serrate-2. Our findings suggest that Notch signals are specifically repressed in the myotome and that asymmetric expression of Numb in dividing cells of the dorsomedial lip of the dermomyotome may modulate whether these cells continue to divide or differentiate into myotomal cells.