Developmental changes in human cerebellum: Expression of intracellular calcium receptors, calcium-binding proteins, and phosphorylated and nonphosphorylated neurofilament protein


  • Ana Milosevic,

    Corresponding author
    1. Department of Neurology, University of Connecticut Health Center, Farmington, Connecticut 06030–1840
    2. Institute for Biological Research, 11000 Belgrade, Yugoslavia
    • University of Connecticut Health Center, Department of Neurology, 263 Farmington Avenue, Farmington, CT 06030–1840
    Search for more papers by this author
  • Nada Zecevic

    1. Department of Neurology, University of Connecticut Health Center, Farmington, Connecticut 06030–1840
    Search for more papers by this author


Few recent data are available on the development of the precise projection maps of the cerebellar cortex in humans. To address this topic, we studied temporal and spatial distribution of several antigens involved in calcium (Ca)-dependent processes: the intracellular Ca receptors, inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) and ryanodine receptor (RyR); the Ca-binding proteins, calbindin D-28k (CB), parvalbumin (PV), and synaptophysin; and phosphorylated (SMI 31) and nonphosphorylated (SMI 32) forms of neurofilament protein. All antigens were studied in the human cerebellum during intrauterine development. The results of this study show that immunocytochemical markers appeared in the 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.w., a diffuse immunostaining for IP3R1 and synaptophysin were observed at 13 g.w., whereas RyR was observed at 17–18 g.w. From 24 g.w. on, Purkinje cells expressed all four examined markers of intracellular Ca signaling as well as two forms of neurofilament protein. At the same time, compartmentation of the Purkinje cell layer was detected with three intracellular Ca-signaling molecules (IP3R1, CB, and PV) and with SMI 32. These results indicate that the developmentally regulated expression of antigens studied here may play a role in establishing a highly regular organization of terminal fields in the human cerebellar cortex. Moreover, the initial expression of these antigens is correlated temporally with other developmental processes in the cerebellum, such as cellular maturation, revealed by the immunoreaction to cytoskeletal protein, and synaptogenesis, revealed by immunoreaction to synaptophysin. J. Comp. Neurol. 396:442–460, 1998. © 1998 Wiley-Liss, Inc.