Early Human Development 54 (1999) 103–116 Calcium signaling molecules in human cerebellum at midgestation and in ataxia a, a b * Nada Zecevic , Ana Milosevic , Barbara E. Ehrlich a Department of Neurology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1840, USA b Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06215, USA Accepted 18 September 1998 Abstract A fundamental question in brain development is how neurons make the precise topographic 21 connections necessary for function. The hypothesis that transient expression of calcium (Ca ) signaling molecules may have a role in this process was tested by studying human cerebella at midgestation. In addition, four adult brains, two controls and two from patients with ataxia, 21 were studied as well. The temporal and spatial distribution of intracellular Ca channel / receptors, inositol trisphosphate receptor type 1 (IP3R1) and ryanodine receptor (RyR) and 21 three Ca binding proteins were examined with immunocytochemical methods. A positive 21 immune reaction with all markers of Ca signaling was found in the Purkinje cell layer starting from 17 g.w. (gestational weeks), the youngest age studied. The immune reactions were not homogeneous throughout the extent of the Purkinje cell layer, but instead displayed a 21 ‘patchy’ appearance in all intrauterine stages. In the adult cerebellum the expression of Ca signaling molecules was homogenous. In the two cerebella obtained from patients suffering from ataxia, a several-fold reduction of immunostaining with IP3R1 was found. Our findings 21 suggest that transient and differential mobilization of intracellular Ca in seemingly homogenous neuronal types may play a role in development of highly organized projection maps of the cerebellar cortex. Moreover, lack of IP3R1 in the diseased brains suggests that 21 internal stores of Ca play an important role in normal function of the cerebellum.  1999 Elsevier Science Ireland Ltd. All rights reserved. 21 Keywords: Ataxia; Ca binding proteins; Cerebellar compartmentalization; Human; Immuno- 21 histochemistry; Intracellular Ca receptor * Corresponding author. Tel.: 1 1-203-679-1768; fax: 1 1-203-679-4446; e-mail: nzecevic@cortex.uchc.edu 0378-3782 / 99 / $ – see front matter  1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S0378-3782(98)00090-5