A1 DEMONSTRATES RESTRICTED TISSUE DISTRIBUTION DURING EMBRYONIC-DEVELOPMENT AND FUNCTIONS TO PROTECT AGAINST CELL-DEATH

Members of the bcl-2 gene family are essential regulators of cell surv ival in a wide range of biological processes, Al, a member of the fami ly, is known to be expressed is certain adult tissues. However, the pr ecise tissue distribution and function of Al remains poorly understood . We show here that Al is expressed is multiple tissues during murine embryonic development. In the embryo, Al was detected first at embryon ic day 11.5 in fiver, brain, and limbs, At day 13.5 of gestation, Al e xpression was observed is the central nervous system, liver, perichond rium, and digital zones of developing limbs in a pattern different fro m that of bcl-X. ln the central nervous system of 15.5-day embryos, Al was expressed at high levels in the ventricular zone and cortical pla te of brain cortex, Significantly, the interdigital zones of limbs and the intermediate region of the developing brain cortex, two sites ass ociated with extensive cell death, were devoid of Al and bcl-X. The ex pression of Al was retained in many adult tissues. To assess the abili ty of Al to modulate cell death, stable transfectants expressing diffe rent amounts of Al protein were generated is K562 cells. Expression of Al was associated with retardation of apoptotic cell death induced by actinomycin D and cycloheximide as well as by okadaic acid, Confocal microscopy showed that the Al protein was localized to the cytoplasm i n a pattern similar to that of Bcl-2. These results demonstrate that t he expression of Al is wider than previously reported It adult tissues . Furthermore, its distribution ill multiple tissues of the embryo sug gests that Al plays a role in the regulation of physiological cell dea th during embryonic development.