LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain.

Area of Science:

• Neuroscience
• Epigenetics
• Developmental Biology

Background:

• Epigenetic complexes regulate neural stem cell (NSC) proliferation and differentiation.
• The role of specific cofactors in guiding histone demethylase LSD1/KDM1A complexes in cortical neurogenesis is not fully understood.

Purpose of the Study:

• To investigate the role of Rcor2, a co-repressor of LSD1, in the epigenetic regulation of cortical development.
• To elucidate how Rcor2 influences neural stem cell proliferation and progeny specification.

Main Methods:

• Analysis of Rcor2 expression in the central nervous system (CNS).
• Depletion studies of Rcor2 to observe effects on NPC proliferation, neuron population, neocortex thickness, and brain size.
• Identification of Rcor2 target genes (Dlx2 and Shh) and assessment of their expression levels.
• Inhibition of Shh signaling to rescue neurogenesis defects.

Main Results:

• Rcor2 is primarily expressed in the CNS and is vital for cortical development.
• Rcor2 depletion leads to decreased NPC proliferation, reduced neuron populations, thinner neocortex, and smaller brain size.
• Rcor2 directly targets and represses Dlx2 and Shh expression in the developing neocortex.
• Inhibition of Shh signaling rescues neurogenesis defects caused by Rcor2 depletion both in vivo and in vitro.

Conclusions:

• Co-repressor Rcor2 is essential for proper cortical development.
• Rcor2 functions by repressing the Shh signaling pathway in the dorsal telencephalon.
• These findings highlight Rcor2's critical role in epigenetic control of neurogenesis.