First Author | Tung YT | Year | 2015 |
Journal | Cell Rep | Volume | 11 |
Issue | 8 | Pages | 1305-18 |
PubMed ID | 26004179 | Mgi Jnum | J:228446 |
Mgi Id | MGI:5707104 | Doi | 10.1016/j.celrep.2015.04.050 |
Citation | Tung YT, et al. (2015) Mir-17 approximately 92 Governs Motor Neuron Subtype Survival by Mediating Nuclear PTEN. Cell Rep 11(8):1305-18 |
abstractText | 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 approximately 92 cluster is enriched in embryonic stem cell (ESC)-derived LMC-MNs and that conditional mir-17 approximately 92 deletion in MNs results in the death of LMC-MNs in vitro and in vivo. mir-17 approximately 92 overexpression rescues MNs from apoptosis, which occurs spontaneously during embryonic development. PTEN is a primary target of mir-17 approximately 92 responsible for LMC-MN degeneration. Additionally, mir-17 approximately 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. |