Modulation of intestinal crypt fission in the rat

Crypt fission, the longitudinal splitting of intestinal crypts, was first noted almost 100 years ago, but has received only a modest amount of attention. Although fissioning crypts have been observed by a number of investigators and referred to by different terms (splitting bifurcating, branching) the full significance of their occurrence has not been established. The aims of this investigation were to: (1) verify that crypt fission is responsible for the formation of new crypts, (2) determine if crypt fission is a local or systemic response to intestinal trauma, and (3) determine if changes in crypt cell proliferation, crypt number, crypt density, or any combination of these factors, operate to modulate crypt fission. These studies can be grouped into two general categories: (1) those based on the response to intestinal injury which include radiation injury, resection of 70% of the small bowel, and treatment with the cytotoxic drugs mechlorethamine and cyclophosphamide, (2) those based on the modification of the crypt cell proliferation rate with possible influences on the naturally high incidence of crypt fission in the juvenile rat. The results from this investigation showed that: (1) crypts of the juvenile and adult rat were formed by crypt fission, (2) crypt fissionmore » was initiated by a reduction in crypt density, (3) crypt fission was under local control, which was related to crypt density, (4) a substantial reduction in the rate of crypt cell proliferation caused no change in the percentage of crypt fission but prevented the formation of new crypts, probably by preventing the fissure from traversing the length of the crypt.« less