MiR-9*- and miR-124a-Mediated Switching of Chromatin Remodelling Complexes is Altered in Rat Spina Bifida Aperta

Abstract

Neural tube defects (NTDs) are complex congenital malformations resulting from incomplete neurulation. Our previous work has demonstrated that motor and sensory neurons develop defectively in rat embryos with spina bifida aperta. To identify whether neural development-associated miRNAs play a role in the neurological deficits of NTDs, we screened a panel of neural development-related miRNAs, including miR-9, miR-9*, miR-124a, miR-10a, miR10b, miR-34a, miR-221 and miR-222, in the spinal cords of rats with retinoic acid-induced spina bifida aperta. We discovered that the expression of miR-9, miR-9* and miR-124a was specifically down-regulated compared to spinal cords without spina bifida. To further clarify whether down-regulation of miR-9* and miR-124a contributes to the neurological deficits of NTDs, we investigated the levels of genes involved in switching in the subunit composition of Swi/Snf-like BAF (Brg/Brm associated factor) complexes modulated by miR-9* and miR-124a and neuronal differentiation. In addition to the down-regulation of miR-9* and miR-124a expression, we also observed increased expression of repressor element silencing transcription factor (REST) and BAF53a and decreased expression of BAF53b, Brg1 and NeuroD1. Our results suggest that REST-regulated miR-9*- and the miR-124a-mediated chromatin remodelling regulatory mechanism may participate in the neuronal deficits of spina bifida.