| Summary: | 博士 === 國立臺灣大學 === 生物科技研究所 === 107 === Long noncoding RNAs (lncRNAs) are an emerging new class of mediator that regulate epigenetics and gene expression. However, only a small set of lncRNAs have been examined in vivo through genetic deletion in animal models (Sauvageau et al., 2013). Additionally, it remains elusive whether lncRNAs function to regulate gene expressions in the central nervous system (CNS). In my PhD study, I explored the lncRNAs that were essential for spinal cord development by profiling cell types at each stage during embryonic stem cell (ESC) differentiation into motor neurons (MNs). Among the lncRNAs candidates, I uncovered that three lncRNAs Meg3 (i.e., Gtl2), Rian and Mirg, which are expressed from the maternally inherited homolog in Dlk1-Dio3 imprinted locus (Lin et al., 2003a), are predominantly and gradually enriched in rostral motor neurons. Although Meg3 has well-characterized functions in stem cell and tumor contexts, its role during motor neuron development is unknown. A recent study revealed that Meg3, Rian and Mirg facilitate Ezh2 and Jarid2 interaction to direct H3K27 trimethylation (H3K27me3) in vitro (Kaneko et al., 2014b). In my study, I found that loss of these lncRNAs compromises the H3K27me3 landscape, leading to aberrant expression of progenitor and caudal Hox genes in postmitotic MNs. My results thus illustrate that these lncRNAs in the Dlk1-Dio3 locus, particularly Meg3, play a critical role in maintaining postmitotic MN cell fate. They shape MN subtype identity by repressing progenitor genes as well as regulating caudal Hox genes. All together, these findings not only provide critical information in regards to lncRNA function, but also in understanding the specific role of lncRNAs during motor neuron development.
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