Novel primate miRNAs coevolved with ancient target genes in germinal zone-specific expression patterns

Area of Science:

• Developmental Neuroscience
• Molecular Biology
• Primate Brain Evolution

Background:

• Cortical development in primates differs significantly from non-primates in germinal zone (GZ) dimensions, cell lineages, and timing.
• MicroRNAs (miRNAs) are key regulators of gene expression, playing critical roles in cellular differentiation and development.

Purpose of the Study:

• To investigate the unique miRNA profiles within distinct germinal zone compartments of the embryonic macaque visual cortex.
• To identify the role of primate-specific miRNAs in regulating cell proliferation and neurogenesis during corticogenesis.

Main Methods:

• Laser-dissection of germinal zone (GZ) compartments and cortical plate (CP) from embryonic macaque visual cortex (area 17).
• Deep sequencing of microRNAs (miRNAs) from dissected tissues.
• Bioinformatic analysis to identify differentially expressed miRNAs and their targets.

Main Results:

• Distinct miRNA profiles were observed in the cortical plate (CP), ventricular zone (VZ), and outer/inner sub-regions of the outer subventricular zone (OSVZ).
• Primate-specific miRNAs, absent in rodents, significantly contributed to differential gene expression between GZ subregions.
• Validated targets of these miRNAs included crucial regulators of cell-cycle and neurogenesis.

Conclusions:

• Emergent miRNAs co-evolved with their targets, integrating into ancient gene networks to control proliferation.
• Cell-cycle regulation by novel miRNAs is essential for primate-specific cortical features, such as the OSVZ.
• The OSVZ and enlarged supragranular layers, regulated by these miRNAs, are linked to enhanced primate computational abilities.