Control of life, death, and differentiation in cultured midgut cells of the lepidopteran, Heliothis virescens

Differentiated cells in the insect midgut depend on stem cells for renewal. We have immunologically identified Integrin a promotor of cell-cell adhesi on that also induces signals mediating proliferation, differentiation, and apoptosis on the surfaces of cultured Heliothis virescens midgut cells; clu sters of immunostained integrin beta (1)-like material, indicative of activ ated integrin, were detected on aggregating midgut columnar cells. Growth f actor-like peptides (midgut differentiation factors 1 and 2 [MDF] and MDF2] ), isolated from conditioned medium containing Manduca sexta midgut cells, may be representative of endogenous midgut signaling molecules. Exposing th e cultured midgut cells to Bacillus thuringiensis (Bt) toxin caused large n umbers of mature differentiated cells to die, but the massive cell death si multaneously induced a 150-200% increase in the numbers of midgut stem and differentiating cells. However, after the toxin was washed out, the proport ions of cell types returned to near-control levels within 2 d, indicating e ndogenous control of cell-population dynamics. MDF1 was detected immunologi cally in larger numbers of Bt-treated columnar cells than controls, confirm ing its role in inducing the differentiation of rapidly produced stem cells . However, other insect midgut factors regulating increased proliferation, differentiation, as well as inhibition of proliferation and adjustment of t he ratio of cell types, remain to be discovered.