Toxic effects of beta-aminopropionitrile treatment on developing chicken skin

beta-aminopropionitrile (BAPN), a compound that inhibits crosslinking of collagen, has been widely used to examine the function of collagen in developing tissues. We used BAPN to examine the function of collagen during the formation and patterning of feather rudiments in embryonic chicken skin. Organ cultures of skin were treated with different concentrations of BAPN and examined for changes in morphology, histology, and extent of collagen crosslinkage. Increasing concentrations of BAPN led to striped patterns of feather rudiments, increases in feather rudiment diameter, and increases in skin thickness in cultured skin. These changes in morphology were paralleled by a progressive decrease in collagen crosslinkage as the concentration of BAPN was increased. However, these changes were also paralleled by an increase in cell death in the epidermis. Culture of monolayers of separated epidermal and dermal cells in the same concentration range of BAPN that altered feather development in the organ cultures showed that BAPN killed epidermal cells but not dermal cells. Our results suggest that developmental alterations caused by BAPN may, in some cases, be due to acute toxicity to specific cell types, and not simply to inhibition of collagen crosslinkage.