DEVELOPMENTAL-CHANGES IN HUMAN CEREBELLUM - EXPRESSION OF INTRACELLULAR CALCIUM RECEPTORS, CALCIUM-BINDING PROTEINS, AND PHOSPHORYLATED ANDNONPHOSPHORYLATED NEUROFILAMENT PROTEIN

Few recent data are available on the development of the precise projec tion maps of the cerebellar cortex in humans. To address this topic, w e studied temporal and spatial distribution of several antigens involv ed in calcium (Ca)-dependent processes: the intracellular Ca receptors , inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) and ryanodine r eceptor (RyR); the Ca-binding proteins, calbindin D-28k (CB), parvalbu min (PV), and synaptophysin; and phosphorylated (SMI 31) and nonphosph orylated (SMI 32) forms of neurofilament protein. All antigens were st udied in the human cerebellum during intrauterine development. The res ults of this study show that immunocytochemical markers appeared in th e following sequence: CB and both forms of neurofilament protein were observed at 4-5 gestational weeks (g.w.), PV appeared in the external granular layer and in a few Purkinje cells at 11 g. rv., a diffuse imm unostaining for IP3R1 and synaptophysin were observed at 13 g.w. where as RyR was observed at 17-18 g.w. From 24 g.w. on, Purkinje cells expr essed all four examined markers of intracellular Ca signaling as well as two forms of neurofilament protein. At the same time, compartmentat ion of the Purkinje cell layer was detected with three intracellular C a-signaling molecules (IP3R1, CB, and PV) and with SMI 32. These resul ts indicate that the developmentally regulated expression of antigens studied here may play a role in establishing a highly regular organiza tion of terminal fields in the human cerebellar cortex. Moreover, the initial expression of these antigens is correlated temporally with oth er developmental processes in the cerebellum, such as cellular maturat ion, revealed by the immunoreaction to cytoskeletal protein, and synap togenesis, revealed by immunoreaction to synaptophysin. (C) 1998 Wiley -Liss, Inc.