Bmp-4 requires the presence of the digits to initiate programmed cell death in limb interdigital tissues

The effects of Bmp-4 on interdigital cell death were investigated in the mo use. Affi-Gel beads, loaded with recombinant Bmp-4 protein, were transplant ed into the interdigital tissues of day 12.5 hindlimb, ex utero. It was est ablished that Bmp-4 could induce precocious interdigital cell death. Using in situ hybridization, the expression patterns of bmp-4 and alk-6 receptor were established. Both genes were found coexpressed in the interdigital reg ion of 12.5- and 13.5-day hindlimbs. This suggests that Bmp-4 may act in an autocrine fashion. We have also studied the effects of Bmp-4 on 12.5-day i nterdigital tissue cultures. In all specimens examined, the interdigital ti ssues produced cartilage instead of participating in cell death. The additi on of exogenous Bmp-4 to the interdigital cultures did not induce apoptosis but instead enhanced chondrogenesis. The discrepancy between the effects o f Bmp-4 in vitro and ex utero was attributed to the presence of digits. Whe n a nanking digit was left attached to the interdigital tissues, in vitro, Bmp-4 promoted apoptosis instead of chondrogenesis. In sum, the results sug gest that Bmp-4 is a multifunctional protein and its effect on the interdig ital tissues is dependent on the modulating influence of the digits. (C) 20 00 Academic Press.