Differential expression of four protocadherin alpha and gamma clusters in the developing and adult zebrafish:: DrPcdh2γ but not DrPcdh1γ is expressed in neuronal precursor cells, ependymal cells and non-neural epithelia

Protocadherins are cadherin-like molecules with adhesive and signaling functions, in particular, during neuronal development. Large protocadherin (Pcdh) gene clusters are present in the genome of vertebrates. In the zebrafish, two Pcdh clusters are found on chromosomes 10 (DrPcdh1) and 14 (DrPcdh2), each divided into subclusters of DrPcdh alpha and DrPcdh gamma family genes. In total, about 100 different DrPcdh molecules are predicted. We have analyzed the expression of the four DrPcdh subclusters and find that DrPcdh transcripts are upregulated in the developing zebrafish nervous system. In the adult fish brain, all four DrPcdh clusters are expressed in differentiated neurons, in particular, in the thalamic nuclei, tectum, and cerebellum. We show that expression patterns grossly overlap for each cluster but with regional differences and variations in strength of expression. Strikingly, the DrPcdh2 gamma cluster, distinct from the three other clusters, is also expressed in neuronal precursor cells and ependymal cells of the embryonic and adult nervous system, as well as in specific non-neuronal epithelia. Antibodies to a conserved motif in the constant region of DrPcdh2 gamma stain fiber tracts and neuropil of the zebrafish brain and cell-cell junctions in epithelia. Our results indicate that multiple DrPcdhs of the different clusters are expressed in differentiated zebrafish neurons, suggesting evolutionarily conserved functions of protocadherin clusters in cell adhesion and signaling. In addition, DrPcdh2 gamma may exert more specific roles in neuronal precursor and non-neural epithelial cells, which have not yet been described for mammalian Pcdh gamma. Thus, our findings in zebrafish open new perspectives to examine these functions in other vertebrate model organisms.