Developmental regulation of Thy 1.2 rate of synthesis in the mouse cerebellum

Thy 1.2 is a well-known major cell surface glycoprotein of the central nervous system (CNS). However, the regulation of the expression of this molecule as well as its function are yet to be determined. To approach these problems we studied the synthesis of the molecule in the developing cerebellum of wild-type and staggerer mutant mice. We found the appearance of a [35S]-methionine-labeled band detected with specific Sepharose 4B-bound monoclonal antibodies (Mabs). The Thy 1.2 activity increases progressively from postnatal day 9 (P9), reaching the highest rate at P12, subsequently decreasing sharply at P13, and remaining relatively low up to P16 in the wild type. Comparison of these data to the rates of total protein synthesis reveals a selective developmental regulation of Thy 1.2 expression, at least at the translational level. This correlates quite well with the timing of synaptic stabilization between parallel fibers and Purkinje cell dendritic spines. Furthermore, at P12 Thy 1.2 protein is preferentially located in the synaptosomal fraction. The parallel fiber:Purkinje cell synapsis is not stabilized in the staggerer mutant mouse. At P12 Thy 1.2 synthesis is 30% of the wild type, indicating that the translational regulation of Thy 1.2 is altered in the staggerer mutation.