Institut Pasteur, Developmental Biology Department, F-75015 Paris, France.
Nat Cell Biol. 2012 Apr 15;14(5):467-76. doi: 10.1038/ncb2481.
Understanding how epithelial polarity is established and regulated during tissue morphogenesis is a major issue. Here, we identify a regulatory mechanism important for mesoderm invagination, germ-band extension and transepithelial migration in the Drosophila melanogaster embryo. This mechanism involves the inhibition of the conserved E3 ubiquitin ligase Neuralized by proteins of the Bearded family. First, Bearded mutant embryos exhibited a loss of epithelial polarity associated with an early loss of the apical domain. Bearded regulated epithelial polarity by antagonizing neuralized. Second, repression of Bearded gene expression by Snail was required for the Snail-dependent disassembly of adherens junctions in the mesoderm. Third, neuralized was strictly required to promote the downregulation of the apical domain in the midgut epithelium and to facilitate the transepithelial migration of primordial germ cells across this epithelium. This function of Neuralized was independent of its known role in Notch signalling. Thus, Neuralized has two distinct functions in epithelial cell polarity and Notch signalling.
了解上皮极性在组织形态发生过程中是如何建立和调节的，是一个主要问题。在这里，我们确定了一个在黑腹果蝇胚胎中对中胚层内陷、胚带延伸和上皮细胞迁移至关重要的调控机制。该机制涉及 Bearded 家族蛋白抑制保守的 E3 泛素连接酶 Neuralized。首先，Bearded 突变体胚胎表现出上皮极性的丧失，伴随着顶端结构域的早期丧失。Bearded 通过拮抗 Neuralized 来调节上皮极性。其次，Snail 通过抑制 Bearded 基因的表达来抑制黏着连接的解聚，这是 Snail 依赖性的。第三，神经源性蛋白在中肠上皮细胞中下调顶端结构域和促进原始生殖细胞穿过该上皮细胞的上皮细胞迁移中是严格必需的。神经源性蛋白的这个功能不依赖于其在 Notch 信号中的已知作用。因此，神经源性蛋白在上皮细胞极性和 Notch 信号中有两个不同的功能。
