Different spatiotemporal expression of DOC2 genes in the developing rat brain argues for an additional, nonsynaptic role of DOC2B in early development

DOC2A and DOC2B are two homologous genes implicated in synaptic vesicle exo cytosis. Their complementary, nonoverlapping expression patterns in adult r at brain suggest that they exert similar functions in different neurons. We have analysed the expression pattern of the two genes in the developing ra t brain by in situ hybridization. Unexpectedly, we found no parallel expres sion of the two genes during development. DOC2B mRNA was highly expressed a s early as embryonic day 12 (E12) throughout the neuroepithelium, long befo re synaptic transmission is functional, and the expression remained abundan t from E12 onwards. In contrast, faint expression of DOC2A transcripts was first detected at E17 in ventral brain areas, and it extended gradually to other brain structures in the sequence of their ontology, i.e. structures t hat had formed first also expressed DOC2A first. At postnatal day 3, both g enes were highly expressed throughout the brain. This overlapping expressio n diverged to the complementary distribution of the adult brain. The tempor al and spatial differences in expression point to a functional divergence b etween these homologous genes during brain development: the pattern of DOC2 A is consistent with its proposed synaptic function, whereas that of DOC2B suggests an additional, nonsynaptic role in proliferating cells.