Ontogenic development and distribution of mRNAs of chromogranin A and B, secretogranin II, p65 and synaptin/synaptophysin in rat brain.
We have studied by in situ hybridization the mRNA levels of several constituents of transmitter storing vesicles during ontogenic development of rat brain. The following vesicle components were investigated: chromogranin A and B and secretogranin II, representing secretory peptides of large dense core vesicles, and the membrane proteins p65 and synaptin/synaptophysin which are found in both large and small synaptic vesicles but are concentrated in the latter ones. Several ontogenic patterns were observed: concomitant increases of most or all mRNAs in certain brain regions, e.g. in the thalamic nuclei at gestational day 18 or in the cortex at postnatal day 6. For some areas selective increases for the various chromogranin mRNAs occurred, thus throughout development the substantia nigra compacta contained only the chromogranin B mRNA, whereas the lateral and medial geniculate nuclei and the medial tuberal nucleus expressed only secretogranin II mRNA. In the paraventricular hypothalamic nucleus, secretogranin II mRNA declined at P1 and then increased again. In the intermediate cortex there was a rather selective appearance of a high level of chromogranin A mRNA already at gestational day 16. In general the mRNAs for the membrane components become detectable by in situ hybridization together with the chromogranin mRNA, however, in the claustrum a high level of the p65 mRNA is present already at gestational day 16 whereas the chromogranin mRNA only appears at day 20. In some nuclei there was also a differential expression of the membrane components with e.g. the synaptophysin mRNA being present without any concomitant appearance of p65. These results establish that the ontogenic development of the investigated components in many brain areas simply indicate the starting point of biosynthesis of both types of vesicles finally leading to functional synapses. In those cases where a selective dissociation in the biosynthesis of these components occurs, a functional relevance of one component for a certain stage of development might be postulated. Since these data define the time of onset of vesicle biosynthesis in the various brain regions, future studies on single components of these vesicles can be interpreted in the context of the present findings.