Mcm5 Represses Endodermal Migration through Cxcr4a-itgb1b Cascade Instead of Cell Cycle Control.

Minichromosome maintenance protein 5 (MCM5) is a critical cell cycle regulator; its role in DNA replication is well known, but whether it is involved in the regulation of organogenesis in a cell cycle-independent way, is far from clear. In this study, we found that a loss of function resulted in a mildly smaller liver, but that overexpression led to liver bifida. Further, the data showed that overexpression delayed endodermal migration in the ventral-dorsal axis and induced the liver bifida. Cell cycle analysis showed that a loss of function, but not overexpression, resulted in cell cycle delay and increased cell apoptosis during gastrulation, implying that liver bifida was not the result of a cell cycle defect. In terms of its mechanism, our data proves that represses the expression of , which sequentially causes a decrease in the expression of during gastrulation. The downregulation of the cascade leads to an endodermal migration delay during gastrulation, as well as to the subsequent liver bifida during liver morphogenesis. In conclusion, our results suggest that in a cell cycle-independent way, works as a gene expression regulator, either partially and directly, or indirectly repressing the expression of and the downstream gene , to coordinate endodermal migration during gastrulation and liver location during liver organogenesis.