Meng Yue, Cai Kathy Q, Moore Robert, Tao Wensi, Tse Jeffrey D, Smith Elizabeth R, Xu Xiang-Xi
Department of Cell Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.
Graduate Program in Molecular Cell and Developmental Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.
Dev Dyn. 2017 Jul;246(7):517-530. doi: 10.1002/dvdy.24503. Epub 2017 May 18.
Phosphatase and tensin homologue on chromosome 10 (Pten), a lipid phosphatase originally identified as a tumor-suppressor gene, regulates the phosphoinositol 3 kinase signaling pathway and impacts cell death and proliferation. Pten mutant embryos die at early stages of development, although the particular developmental deficiency and the mechanisms are not yet fully understood.
We analyzed Pten mutant embryos in detail and found that the formation of the proamniotic cavity is impaired. Embryoid bodies derived from Pten-null embryonic stem cells failed to undergo cavitation, reproducing the embryonic phenotype in vitro. Analysis of embryoid bodies and embryos revealed a role of Pten in the initiation of the focal point of the epithelial rosette that develops into the proamniotic lumen, and in establishment of epithelial polarity to transform the amorphous epiblast cells into a polarized epithelium.
We conclude that Pten is required for proamniotic cavity formation by establishing polarity for epiblast cells to form a rosette that expands into the proamniotic lumen, rather than facilitating apoptosis to create the cavity. Developmental Dynamics 246:517-530, 2017. © 2017 Wiley Periodicals, Inc.
10号染色体上的磷酸酶和张力蛋白同源物(Pten)是一种最初被鉴定为肿瘤抑制基因的脂质磷酸酶,它调节磷酸肌醇3激酶信号通路,并影响细胞死亡和增殖。Pten突变胚胎在发育早期死亡,尽管其具体的发育缺陷和机制尚未完全了解。
我们详细分析了Pten突变胚胎,发现羊膜腔的形成受损。源自Pten基因缺失的胚胎干细胞的类胚体未能发生空化,在体外重现了胚胎表型。对类胚体和胚胎的分析揭示了Pten在发育成羊膜腔的上皮玫瑰花结焦点起始过程中的作用,以及在建立上皮极性以将无定形的上胚层细胞转化为极化上皮过程中的作用。
我们得出结论,Pten是羊膜腔形成所必需的,它通过为上胚层细胞建立极性以形成扩展为羊膜腔的玫瑰花结,而不是促进细胞凋亡来形成腔。《发育动力学》246:517 - 530,2017年。©2017威利期刊公司。