Neuroepithelial cell competition triggers loss of cellular juvenescence

Cell competition is a cell–cell interaction mechanism which maintains tissue homeostasis through selective elimination of unfit cells. During early brain development, cells are eliminated through apoptosis. How cells are selected to undergo elimination remains unclear. Here we aimed to identify a role for cell competition in the elimination of suboptimal cells using an in vitro neuroepithelial model. Cell competition was observed when neural progenitor HypoE-N1 cells expressing RASV12 were surrounded by normal cells in the co-culture. The elimination through apoptosis was observed by cellular changes of RASV12 cells with rounding/fragmented morphology, by SYTOX blue-positivity, and by expression of apoptotic markers active caspase-3 and cleaved PARP. In this model, expression of juvenility-associated genes Srsf7 and Ezh2 were suppressed under cell-competitive conditions. Srsf7 depletion led to loss of cellular juvenescence characterized by suppression of Ezh2, cell growth impairment and enhancement of senescence-associated proteins. The cell bodies of eliminated cells were engulfed by the surrounding cells through phagocytosis. Our data indicates that neuroepithelial cell competition may have an important role for maintaining homeostasis in the neuroepithelium by eliminating suboptimal cells through loss of cellular juvenescence.

Redundant type II cadherins define neuroepithelial cell states for cytoarchitectonic robustness

Individual cell shape and integrity must precisely be orchestrated during morphogenesis. Here, we determine function of type II cadherins, Cdh6, Cdh8, and Cdh11, whose expression combinatorially demarcates the mouse neural plate/tube. While CRISPR/Cas9-based single type II cadherin mutants show no obvious phenotype, Cdh6/8 double knockout (DKO) mice develop intermingled forebrain/midbrain compartments as these two cadherins’ expression opposes at the nascent boundary. Cdh6/8/11 triple, Cdh6/8 or Cdh8/11 DKO mice further cause exencephaly just within the cranial region where mutated cadherins’ expression merges. In the Cdh8/11 DKO midbrain, we observe less-constricted apical actin meshwork, ventrally-directed spreading, and occasional hyperproliferation among dorsal neuroepithelial cells as origins for exencephaly. These results provide rigid evidence that, by conferring distinct adhesive codes to each cell, redundant type II cadherins serve essential and shared roles in compartmentalization and neurulation, both of which proceed under the robust control of the number, positioning, constriction, and fluidity of neuroepithelial cells.

Neuroepithelial Cell Transforming Gene 1 Acts as an Oncogene and Is Mediated by miR-22 in Human Non-Small-Cell Lung Cancer

Abnormal expression of neuroepithelial cell transforming gene 1 (NET1) has been authenticated in many human cancers, including lung cancer. We have previously reported that NET1 functioned as an oncogene and promoted human non-small-cell lung cancer (NSCLC) growth and migration. However, the correlation between NET1 and its upstream miRNAs needed further illustration. Our present work demonstrated that miR-22 had a relatively low expression, and NET1 had a relatively high expression in both NSCLC samples and lung adenocarcinoma cell lines compared with corresponding normal controls. Moreover, miR-22 directly regulated NET1 and was verified to weaken cancer cell proliferation and migration, as well as enhance cell apoptosis by suppressing NET1. Furthermore, the inhibitory effect of miR-22 can be reversed via overexpressing NET1 using an ectopic expression vector in NSCLC cells. Our findings showed that miR-22/NET-1 axis may contribute to the inhibition of NSCLC growth and migration and represents a promising therapeutic target for NSCLC.