aPKC, Crumbs3 and Lgl2 control apicobasal polarity in early vertebrate development
aPKC, Crumbs3 and Lgl2 control apicobasal polarity in early vertebrate development
复制标题
DOI：
10.1242/dev.01645
复制
发表时间：
2005-03-01
期刊：
影响因子：
4.6
通讯作者：
Papalopulu, N
中科院分区：
文献类型：
--
作者：
Chalmers, AD;Pambos, M;Papalopulu, N
在早期脊椎动物发育中，顶基极化的卵裂球分裂产生内部非极化细胞和外部极化细胞，它们的命运不同。这些早期卵裂球的极性是如何形成的尚不清楚。我们研究了Crumbs3、Lg12和顶端aPKC在青蛙卵裂球极化中的作用。Lg12定位于卵裂球的基底外膜，而crums3定位于卵裂球的顶膜和基底外膜。aPKC和crumb3的过表达以基底外侧为代价扩展了根尖结构域，并重新定位了新的根尖-基底外侧界面的紧密连接。aPKC功能的丧失导致根尖标记物的丢失，并将基底外侧标记物定向到异位的根尖膜。细胞极性和紧密连接（而不是细胞粘附）丧失，外部极化细胞变成内部样极性细胞。非洲爪蟾Lg12的过表达导致aPKC基因敲除，表明Lg12和aPKC具有拮抗作用。这证实了aPKC和Lg12可以抑制彼此的定位，Lg12可以挽救aPKC引起的资本化。我们得出结论，aPKC和Lg12之间的拮抗相互作用决定了早期脊椎动物发育的尖基底极性。
In early vertebrate development, apicobasally polarised blastomeres divide to produce inner non-polarised cells and outer polarised cells that follow different fates. How the polarity of these early blastomeres is established is not known. We have examined the role of Crumbs3, Lg12 and the apical aPKC in the polarisation of frog blastomeres. Lg12 localises to the basolateral membrane of blastomeres, while Crumbs3 localises to the apical and basolateral membranes. Overexpression aPKC and Crumbs3 expands the apical domain at the expense of the basolateral and repositions tight junctions in the new apical-basolateral interface. Loss of aPKC function causes loss of apical markers and redirects basolateral markers ectopically to the apical membrane. Cell polarity and tight junctions, but not cell adhesion, are lost and outer polarised cells become inner-like apolar cells. Overexpression of Xenopus Lg12 phenocopies the aPKC knockout, suggesting that Lg12 and aPKC act antagonistically. This was confirmed by showing that aPKC and Lg12 can inhibit the localisation of each other and that Lg12 rescues the apicalisation caused by aPKC. We conclude that an instrumental antagonistic interaction between aPKC and Lg12 defines apicobasal polarity in early vertebrate development.