Research News
Mir-17~92 Governs Motor Neuron Subtype Survival by Mediating Nuclear PTEN
By Dr. Chen, Jun-An - May, 2015 Cell Reports Cover Featured ArticleMotor 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 finetune the balance between survival and apoptosis while wiring the sensorimotor circuit en route remains unclear. Here, we show that the mir-1792 cluster is enriched in embryonic stem cell (ESC)- derived LMC-MNs and that conditional mir-1792 deletion in MNs results in the death of LMC-MNs in vitro and in vivo. mir-1792 overexpression rescues MNs from apoptosis, which occurs spontaneously during embryonic development. PTEN is a primary target of mir-1792 responsible for LMCMN degeneration. Additionally, mir-1792 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.
