title: Mir-17∼92 Governs Motor Neuron Subtype Survival by Mediating Nuclear PTEN.
abstract: 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∼92 cluster is enriched in embryonic stem cell (ESC)-derived LMC-MNs and that conditional mir-17∼92 deletion in MNs results in the death of LMC-MNs in vitro and in vivo. mir-17∼92 overexpression rescues MNs from apoptosis, which occurs spontaneously during embryonic development. PTEN is a primary target of mir-17∼92 responsible for LMC-MN degeneration. Additionally, mir-17∼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.
authors.forename: Ying-Tsen
authors.initials: YT
authors.lastname: Tung
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Lu
authors.forename: Kuan-Chih
authors.initials: KC
authors.lastname: Peng
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Yen
authors.forename: Mien
authors.initials: M
authors.lastname: Chang
authors.forename: Joye
authors.initials: J
authors.lastname: Li
authors.forename: Heekyung
authors.initials: H
authors.lastname: Jung
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thams
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Huang
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Hung
authors.forename: Jun-An
authors.initials: JA
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; D044767:Ubiquitin-Protein Ligases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse