Abstract
Proper growth of the mammalian cerebral cortex, which is determined by expansion and survival of neural progenitors and mature neurons, is crucial for cognitive functions. Here, we show a role of the dosage of microRNA miR-9 in controlling brain size. Cortical-specific upregulation of miR-9 causes microcephalic defects in mice, due to apoptosis, reduced neural progenitor pool, and decreased neurogenesis. Glial cell-derived neurotrophic factor (GDNF) is a target of miR-9, and protects neural progenitors from miR-9-induced apoptosis. Furthermore, Zika virus (ZIKV) infection in embryonic mouse cortex causes reduced numbers in neural progenitors and newborn neurons, and results in upregulation of miR-9, downregulation of its target GDNF. Our studies indicate an association of altered levels of miR-9 and its target GDNF with microcephaly and ZIKV infection in mice.
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