DEVELOPMENTAL PATTERNS OF BCL-2 AND BCL-X POLYPEPTIDE EXPRESSION IN THE HUMAN SPINAL-CORD

The cell death suppressors bcl-2 and bcl-x are developmentally regulat ed and may modulate physiologic cell death in the central nervous syst em (CNS). However, little data are currently available on the expressi on patterns of these polypeptides in the human CNS. We examined the on togeny of bcl-2 and bcl-x in 12 human spinal cords of gestational ages (GA) between 5 and 39 weeks and in 3 adult cords. Paraffin sections w ere probed by immunohistochemistry using well-characterized, commercia lly available antibodies that had been raised against poorly conserved epitopes of these homologous proteins. Between 5 and 10 weeks GA bcl- 2 immunoreactivity was identified in primitive neuroepithelial cells o f the ventricular zone. Individual cells of the mantle zone were stain ed including clusters of early anterior horn cells. Bcl-x immunoreacti vity was most prominent in differentiating neurons of the mantle zone and less pronounced in the ventricular zone. Between 10 and 14 weeks G A, bcl-2 staining was observed in cells lining the central canal, neur ons of the dorsal horn (especially laminae I and II), and in anterior horn cells. The latter exhibited a range of staining intensities from moderate to nondetectable. Bcl-2 immunoreactivity became markedly redu ced between 15 and 25 weeks GA, persisting only in ependymal cells. In contrast, strong bcl-x staining was observed in most neurons througho ut development and into adulthood. The period of apparent bcl-2 downre gulation overlaps with a peak in physiologic motoneuron death and the establishment of functional neuromuscular synapses in the human spinal cord. These findings suggest that bcl-2 and bcl-x may both be require d for survival of early postmitotic neurons before appropriate synapti c connections have been established. Continued neuronal survival (afte r bcl-2 is down-regulated) may require persistent bcl-x expression in addition to target-derived neurotrophic factors made available through the formation of appropriate synapses. (C) 1998 Academic Press.