In Vivo Imaging Reveals Existence of Crypt Fission and Fusion in Adult Mouse Intestine

The intestinal epithelium is a repetitive sheet of crypt and villus units with stem cells at the bottom of the crypts. During postnatal development, crypts multiply via fission, generating 2 daughter crypts from 1 parental crypt. In the adult intestine, crypt fission is observed at a low frequency. Using intravital microscopy in Lgr5EGFP-Ires-CreERT2 mice, we monitored individual crypt dynamics over multiple days with single-cell resolution. We discovered the existence of crypt fusion, an almost exact reverse phenomenon of crypt fission, in which 2 crypts fuse into 1 daughter crypt. Examining 819 crypts in 4 mice, we found that 3.5% ± 0.6% of all crypts were in the process of fission, whereas 4.1 ± 0.9% of all crypts were undergoing crypt fusion. As counteracting processes, crypt fission and fusion could regulate crypt numbers during the lifetime of a mouse. Identifying the mechanisms that regulate rates of crypt fission and fusion could provide insights into intestinal adaptation to altered environmental conditions and disease pathogenesis.