Three tandemly arrayed protocadherin gene clusters (Pcdh-α, -β, -γ) comprising more than 50 genes are found in human and mouse. Here, we have investigated the expression and distribution of individual gamma-protocadherins (Pcdhs-γ) in the developing mouse brain. We find that transfection of Pcdh-γ genes promotes calcium-dependent cell adhesion in HEK 293 cells. Furthermore, Pcdh-γ can be recruited to synapses of transfected primary hippocampal neurons. Several individual members of the in total 22 Pcdhs-γ were chosen to examine the expression of the three subfamilies, Pcdh-γA, -γB, and -γC. These Pcdh-γ transcripts are expressed all over the brain, with minor regional and cell-type specific differences. Interestingly, a distinct, later onset of expression is observed for Pcdh-γC5, a gene located at the end of the Pcdh-γ cluster. Largely overlapping expression patterns of individual Pcdh-γ proteins are detected with anti-peptide antibodies. Small differences are observed in the staining of dendritic processes and synapse-rich layers. Our results support the idea that Pcdhs-γ participate in neuronal differentiation and may be implicated in the fine-tuning of neuronal morphology and synaptogenesis. Cell autonomous regulation of transcription might generate the widespread distribution of individual Pcdhs-γ in the brain, which is strikingly different from the restricted expression patterns observed for classical cadherins. Thus, a defined set of Pcdhs-γ may engage in neuronal adhesion and signaling on the cellular level
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