Spatial and temporal expression of lysosomal acid phosphatase 2 (ACP2) reveals dynamic patterning of the mouse cerebellar cortex.

The Acp2 gene encodes lysosomal acid phosphatase 2 (ACP2), an isoenzyme that hydrolyzes orthophosphoric monoesters to alcohol and phosphate. Mutations in this gene compromise lysosomal function and cause acid phosphatase deficiency. Loss of Acp2 in the brain causes defects in the cerebellum. Here, we performed an in-depth protein expression analysis in the mouse cerebellum to understand how Acp2 controls cellular function in the developing and adult brain. We have found that during development, ACP2 expression marks the caudal midbrain and cerebellum, two regions that are linked by multiple signaling mechanisms during embryogenesis. By around P8, ACP2 was localized predominantly to the somata of Purkinje cells, the principal neurons of the cerebellar cortex. During the second postnatal week, we found that ACP2 expression expanded into the dendrites and axon terminals of Purkinje cells. However, at 2 weeks of age, only a subset of Purkinje cells strongly express ACP2. Further expression analyses revealed that in the mature cerebellum, ACP2 expression divided Purkinje cells into a pattern of molecular zones that are associated with the functional topography of sensory-motor circuitry. These data suggest that ACP2 expression is dynamically regulated during development, and in the adult, it may function within a complex architecture that is linked to cerebellar modular organization.