Upregulation of MicroRNA miR-9 Is Associated with Microcephaly and Zika Virus Infection in Mice

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Proper mammalian cerebral cortex growth is essential for cognitive functions.
• Neural progenitor cell survival and expansion are critical determinants of brain size.

Purpose of the Study:

• To investigate the role of microRNA miR-9 dosage in controlling mammalian brain size.
• To explore the association between miR-9, its target GDNF, and microcephaly, including in the context of Zika virus infection.

Main Methods:

• Investigated the effects of cortical-specific miR-9 upregulation in mice.
• Analyzed neural progenitor numbers, neurogenesis, and apoptosis.
• Examined the impact of Zika virus infection on embryonic mouse cortex.

Main Results:

• Cortical upregulation of miR-9 led to microcephaly, characterized by apoptosis, reduced neural progenitor pool, and decreased neurogenesis.
• Glial cell-derived neurotrophic factor (GDNF) was identified as a miR-9 target, protecting neural progenitors from apoptosis.
• Zika virus infection in embryonic mouse cortex resulted in reduced neural progenitors and newborn neurons, accompanied by miR-9 upregulation and GDNF downregulation.

Conclusions:

• miR-9 dosage is a critical regulator of mammalian brain size.
• Altered miR-9 and GDNF levels are associated with microcephaly and Zika virus infection in mice.