DNA repair during embryonic epidermal stratification

Genomes are constantly exposed to a myriad of DNA-damaging agents. Robust DNA repair mechanisms protect DNA by removing or tolerating damage. However, it remains unclear whether these mechanisms are required for organogenesis.

Multiple epithelial layers are essential for skin function, including body protection. The epidermis is initiated as a single layer and then stratifies in utero. Stratification did not occur in mice with epithelial conditional deletion of the DNA repair molecule Reptin (Reptin^fl/fl;K14Cre). DNA damage was observed in the mutant epidermis but not in the wild-type epidermis. The mutant epidermis also showed reduced cell proliferation and upregulated p53 expression. Stratification was restored when p53 was deleted in the Reptin mutant mice by generating Reptin and p53 double mutant mice (Reptin^fl/fl;K14Cre;p53^-/-).

In the wild-type epidermis, DNA is likely damaged at the initiation of embryonic stratification and promptly repaired by DNA repair mechanisms involving Reptin.