microRNA Expression in the Late Embryonic Pax6-Null Mouse Cerebellum.

Classically, Pax6 is a gene critical for eye development, but more recently, it has been shown to be important for the development of several organ systems including the cerebellum. In the Pax6 mutant cerebellum, there are developmental alterations specific to the glutamatergic neurons. This study investigates the regulatory role of microRNAs (miRNAs), small non-coding RNAs, on mRNAs in wildtype and Pax6-null cerebellar development at embryonic day (E) 18.5. RNAs were extracted and sequenced, establishing the expression profile of both miRNAs and mRNAs. A total of 491 known miRNAs and 262 putative, novel miRNAs met the expression criteria defined for our cerebellar samples. Using bioinformatic tools, 44 significantly differentially expressed (DE) known miRNAs and 60 DE mRNAs were identified between wildtype and Pax6-null tissue. The DE miRNAs identified had high expression correlation with 208 unique mRNA targets in our samples. These target mRNAs and the DE mRNAs were significantly enriched for functions in brain development, particularly relevant to synaptogenesis. Overall, our study adds to the growing body of literature on the functional and mechanistic roles of miRNAs in brain development, from the perspective of key regulatory networks controlled by Pax6.