Variations in gene expression during development of the rat cerebellum.

Prominent variations in the concentration and composition of poly (A)-containing messenger RNA were found to occur during the postnatal development of the rat cerebellum. The concentration of mRNA (microgram/g cerebellar tissue) was determined to be the highest on the tenth postnatal day, at the onset of synaptogenesis. Short non-abundant mRNA chains continuously increase in amount during cerebellar development, while the fraction of long translatable mRNAs decreases. The overall ability of cerebellar mRNA to stimulate the incorporation of [35S]methionine into polypeptides in reticulocyte lysate apparently does not change. The proteins synthesized in vitro by cerebellar mRNA from different developmental stages were therefore analyzed by single and 2-dimensional gel electrophoresis. The diversity of these proteins and the levels of many of them were found to vary with cerebellar development. The newly synthesized brain forms of enolase and creatine kinase were identified by their migration coordinates in the 2-dimensional protein gels, and increase in the abundance of their directing mRNAs was found to accompany the differentiation of cerebellar interneurons. The extent of modification in cerebellar mRNA was determined to be much higher than the consequent changes in the composition of cerebellar proteins. We propose to use the ontogenetic variations in the levels of specific cerebellar mRNA species in normal and malformed cerebellum to identify proteins specific to particular types of cerebellar neurons.