Browsing by Author "Lu, Ya-Lin"

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Dlk1-Dio3 locus-derived lncRNAs perpetuate postmitotic motor neuron cell fate and subtype identity
(2018-10-12)
Yen, Ya-Ping
;
Hsieh, Wen-Fu
;
Tsai, Ya-Yin
;
Lu, Ya-Lin
;
Liau, Ee Shan
The mammalian imprinted Dlk1-Dio3 locus produces multiple long non-coding RNAs (lncRNAs) from the maternally inherited allele, including Meg3 (i.e., Gtl2) in the mammalian genome. Although this locus has well-characterized functions in stem cell and tumor contexts, its role during neural development is unknown. By profiling cell types at each stage of embryonic stem cell-derived motor neurons (ESC similar to MNs) that recapitulate spinal cord development, we uncovered that lncRNAs expressed from the Dlk1-Dio3 locus are predominantly and gradually enriched in rostral motor neurons (MNs). Mechanistically, Meg3 and other Dlk1-Dio3 locus-derived lncRNAs facilitate Ezh2/Jarid2 interactions. Loss of these lncRNAs compromises the H3K27me3 landscape, leading to aberrant expression of progenitor and caudal Hox genes in postmitotic MNs. Our data thus illustrate that these lncRNAs in the Dlk1-Dio3 locus, particularly Meg3, play a critical role in maintaining postmitotic MN cell fate by repressing progenitor genes and they shape MN subtype identity by regulating Hox genes.
Mir-17 similar to 92 Governs Motor Neuron Subtype Survival by Mediating Nuclear PTEN
(2015-05-26)
Tung, Ying-Tsen
;
Lu, Ya-Lin
;
Peng, Kuan-Chih
;
Yen, Ya-Ping
;
Chang, Mien
Motor neurons (MNs) are unique because they project their axons outside of the CNS to innervate the peripheral muscles. Limb-innervating lateral motor column MNs (LMC-MNs) travel substantially to innervate distal limb mesenchyme. How LMC-MNs fine-tune the balance between survival and apoptosis while wiring the sensorimotor circuit en route remains unclear. Here, we show that the mir-17 similar to 92 cluster is enriched in embryonic stem cell (ESC)derived LMC-MNs and that conditional mir-17 similar to 92 deletion in MNs results in the death of LMC-MNs in vitro and in vivo. mir-17 similar to 92 overexpression rescues MNs from apoptosis, which occurs spontaneously during embryonic development. PTEN is a primary target of mir-17 similar to 92 responsible for LMC-MN degeneration. Additionally, mir-17 similar to 92 directly targets components of E3 ubiquitin ligases, affecting PTEN subcellular localization through monoubiquitination. This miRNA-mediated regulation modulates both target expression and target subcellular localization, providing LMC-MNs with an intricate defensive mechanism that controls their survival.