Neurogranin expression identifies a novel array of Purkinje cell parasagittal stripes during mouse cerebellar development

Abstract

Markers that reveal the parasagittal organization of cerebellar Purkinje cells may be grouped into two classes based on the time during development when they are expressed. In mice, early-onset markers are defined by their heterogeneous expression in clusters of Purkinje cells during late embryogenesis, which disappears shortly following birth. Late-onset markers are generally not expressed until about 1 week after birth and do not reach a stable striped expression pattern until about 3 weeks postnatally. Currently, no endogenous markers are known that are heterogeneously expressed in the temporal gap between these two classes. Here we present immunocytochemical evidence that parasagittal stripes of Purkinje cells express a member of the calpacitin protein family, neurogranin, possibly from as early as embryonic day (E) 13 and definitively from E15, in a pattern that persists up to postnatal day (P) 20. Neurogranin is thus the first endogenous marker of a Purkinje cell subset capable of bridging the temporal gap between the early- and late-onset patterns. In the early neonate, up to five pairs of neurogranin-immunopositive Purkinje cell stripes run parasagittally through the cerebellum, with the exact number dependent on the rostrocaudal position. Expression is lost during postnatal development in a transverse zone-dependent fashion. Purkinje cells in the central and nodular zones lose neurogranin expression between approximately P4 and P6, whereas expression in the posterior zone persists until approximately P20. Neurogranin immunoreactivity will be a valuable tool in helping to clarify the relationships between early- and late-onset patterns.