RT Journal Article
SR Electronic
T1 Loss of cell cycle control renders cells nonresponsive to local extrinsic differentiation cues
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 720276
DO 10.1101/720276
A1 Kara L. Cerveny
A1 Ingrid Tower
A1 Dayna B. Lamb
A1 Avery Van Duzer
A1 Hannah Bronstein
A1 Olivia Hagen
A1 Máté Varga
YR 2019
UL http://biorxiv.org/content/early/2019/07/30/720276.abstract
AB Objective and approaches Aberrantly proliferating cells are linked to a number of diseases including cancers and developmental defects.To determine the extent to which local extrinsic signals contribute to or ameliorate mutant cell behaviors, we examined survival and differentiation of mutant cells in wild-type retinal environments by generating chimeric zebrafish embryos comprised of unlabeled host cells and GFP-labeled neural progenitor donor cells. In addition, we examined the fate of retinal progenitor cells when cdkn1c, a cyclin dependent kinase inhibitor, was induced in clones within wild-type and hdac1 mutant retinae.Results We found that seven of the ten mutants examined exhibited apoptosis when grafted into wild-type tissue, with cells from two slowly cycling mutants, elys and emi1, noticeably differentiating in a wild-type environment. Observations of the one hyperproliferative mutant, hdac1, revealed that these mutant cells did not appear to die or differentiate but instead survived and formed tumor-like rosettes in a wild-type environment. Ectopic expression of cdkn1c was unable to force cell cycle exit and differentiation of the majority of hdac1 mutant cells.Conclusions Together, these results suggest that although a wild-type environment rarely encourages cell cycle exit and differentiation of neural progenitors with cell cycle defects, wild-type survival signals may enable hyperproliferative progenitor cells to persist instead of die.