Mir-17~92 Governs Motor Neuron Subtype Survival by Mediating Nuclear PTEN

Ying Tsen Tung, Ya Lin Lu, Kuan Chih Peng, Ya Ping Yen, Mien Chang, Joye Li, Heekyung Jung, Sebastian Thams, Yuan Ping Huang, Jui-Hung Hung, Jun An Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 invitro and invivo. 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.

Original languageEnglish
Pages (from-to)1305-1318
Number of pages14
JournalCell Reports
Volume11
Issue number8
DOIs
StatePublished - 26 May 2015

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