Distribution of protocadherin 9 protein in the developing mouse nervous system.

Protocadherin 9 (Pcdh9) is a member of the protocadherin family, which includes many members involved in various phenomena, such as cell-cell adhesion, neural projection, and synapse formation. Here, we identified Pcdh9 protein in the mouse brain and examined its distribution during neural development. Pcdh9, with a molecular weight of approximately 180 kDa, was localized at cell-cell contact sites in COS-1 cells transfected with Pcdh9 cDNA. In cultured neurons, it was detected at the growth cone and at adhesion sites along neurites. In the E13.5 brain, prominent Pcdh9 immunoreactivity was detected in the dorsal thalamus along with other regions including the vestibulocochlear nerve. As development proceeded (E15.5-P1), Pcdh9 immunoreactivity became observable in various brain regions but was restricted to certain fiber tracts and brain nuclei. Interestingly, many Pcdh9-positive brain nuclei and fascicles belonged to the vestibular (e.g. vestibulocochlear nerve, vestibular nuclei, and the vestibulocerebellum) and oculomotor systems (medial longitudinal fascicles, oculomotor nucleus, trochlear nucleus, and interstitial nucleus of Cajal). In addition, we examined the distribution of Pcdh9 protein in the olfactory bulb, retina, spinal cord, and dorsal root ganglion. In these regions, Pcdh9 and OL-protocadherin proteins were differentially distributed, with the difference highlighted in the olfactory bulb, where they were enriched in different subsets of glomeruli. In the mature retina, Pcdh9 immunoreactivity was detected in distinct sublaminae of the inner and outer plexiform layers. In the dorsal root ganglion, only certain subsets of neurons showed Pcdh9 immunoreactivity. These results suggest that Pcdh9 might be involved in formation of specific neural circuits during neural development.