Transient Increase in Cerebellar Transcriptional Activity Precedes the Expression of GABAA Receptor α6 Subunit mRNA during Postnatal Maturation

The purpose of this study was to investigate the postnatal expression of GABAA receptor α6 subunit genes in the context of cerebellar differentiation. We examined steady-state levels of GABAA receptor α1 and α6 subunit mRNAs, polyadenylated (polyA+) mRNA and β-actin mRNA in7-, 14-, 21-, 28-, 35-, 49- and 120-day-old rats. Messenger RNA expression and splicing were evaluated in parallel using Northern blot analysis and in situ hybridization histochemistry. The expression of mature GABAA receptor α6 subunit mRNA species (2.7 kb) was found 1 week after birth in cerebellar granule cells. Prior to stable expression of the mature α6 subunit gene, we detected large α6 subunit premessengers (3.8 and 3.5 kb) by Northern blot analysis. These premessenger species were detected in prenatal day (PND) 15 and neonatal rat cerebellum, when the mature α6 subunit mRNAs (2.7 kb) were not yet expressed. The maximal expression of mature α6 subunit mRNA species was observed at PND 21 when the peak level of cerebellar transcriptional activity was measured by polyA+ RNA levels. In contrast, β-actin mRNA expression was decreased at PND 21 compared to birth levels. These major transcriptional events take place during a period of about 1 week (between PND 14 and 21), immediately following the most active phase of cell division in the external granule layer and migration of granule cells to the internal granule cell layer. Comparison between the relative abundance of these genes shows that differential regulation of each gene occurs during postnatal development. The induction of GABAA receptor α6 subunit gene expression is preceded by a reduction in β-actin mRNA levels and a transient increase in total transcriptional activity. The expression of α6 subunit mRNA is maintained at the PND 21 level through adulthood, but the α1 subunit mRNA levels decrease drastically within the following week (from PND 21 to 28). These results suggest that tissue-specific expression of the GABAA receptor α6 subunit gene is correlated with a series of developmentally regulated morphologic and transcriptional events.

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