The RNA-binding protein Musashi2 regulates asymmetric neural precursor cell divisions of the developing cerebral cortex
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Abstract
The brain’s complex cortical circuitry is generated through asymmetric divisions of neural precursor cells (NPCs). These divisions produce one NPC plus one differentiated neuron or intermediate progenitor, due in part to localization of fate determinants to a single region of the dividing cell. This research identifies Musashi2 (mMsi2) as a critical component of cortical asymmetric NPC division. Temporal expression profiles and in vitro immunofluorescence detected mMsi2 within NPCs and some neurons of the mouse cortex throughout neurogenesis. shRNA knockdown in cortical primary culture demonstrated that mMsi2 loss increases NPCs and proportionally decreases neurons and intermediate progenitors, while mMsi2 knockdown in utero similarly increased cells within immature layers of the mouse cortex. mMsi2 overexpression in cortical primary culture again increased NPCs, suggesting that developmental mMsi2 expression must be tightly regulated. Together, these results indicate that mMsi2 promotes neuronal formation during asymmetric NPC division, and is therefore essential to cortical development.