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Sexually dimorphic expression of splicing factors in the developing mouse cortex and hippocampus



The cerebral cortex and hippocampus are important for many cognitive functions, several of which are sexually dimorphic. However, the mechanism underlying functional sex differences remain undiscovered. With increasing number of neurological and mental disorders found associated with splicing defects, it has become evident that alternative splicing may play an important role in regulating brain function, especially those served by the cortex and hippocampus. Thus, we hypothesize that sexually dimorphic expression of splicing factors in the developing mouse cortex and hippocampus regulate gene expression post-transcriptionally, resulting in sex-differentiated cognitive function and behavior. To test our hypothesis, we measured mRNA levels of splicing factor 3a, subunit 2 (Sf3a2), polypyrimidine tract-binding protein-associated splicing factor (Sfpq), splicing factor suppressor of white apricot (Sfswap), and serine/arginine-rich splicing factors 1, 3, and 10 (Srsf1, Srsf3, and Srsf10) genes, in the mouse cortex and hippocampus on the day of birth (PN0) and 7 (PN7), 14 (PN14), and 21 (PN21) postnatal using reverse transcription with real-time polychain reaction (RT-qPCR). We found a significant effect of age for all genes but Srsf10, but a significant effect of sex for only Srsf10, Sfswap, and Srsf3 and a sex/age interaction for Sfswap and Srsf3. Our data demonstrate the importance of both age and sex on the expression of splicing factors found in the developing brain, implicating alternative splicing's involvement in controlling the sexual differentiation responsible for noted differences in cognitive behaviors and sex-biased diseases.


sexual differentiation, splicing factor, cortex