Epigenetic control of neuronal polarization and axon growth by G9a and the H3K9me2 label

CARLOS WILSON

Virtual

Simposio; 2021 SBBMCH Annual Meeting; 2021

Sociedad Chilena de Bioquimica y Biologia Molecular

Neurons are polarized cells, exhibiting the somato-dendritic and axonalcompartments; domains specialized in receiving and transmitting signals,respectively. This compartmentalization is the result of decoding extrinsic/intrinsicstimuli, impacting on signaling pathways able to shape the neuronal morphology. Inthis regard, cytoskeleton remodeling is crucial, since both microtubules (MT) and F-actin (FA) represent the driving force of polarization and axonal development.Although polarity mechanisms have been reported, the genetic fundamentals remainunderexplored. Recently, we reported that the histone methyltransferase G9apromotes polarization and axonal growth in cultured hippocampal neurons, byrepressing the RhoA-ROCK pathway, a negative regulator of neuronal polarization. Inaddition, the loss of function of G9a in situ impaired cortical migration of embryonicneurons, suggesting failures on polarization and migration in vivo. Moreover, bi-methylation of H3K9 (H3K9me2), highly dependent on G9a in developing neurons,parallels axon formation in early and mature stages. Accordingly, genetic deletion ofnuclear H3K9me2 impairs axonal maturation, visualized by abnormal assembly of theaxon initial segment (AIS); the intra-axonal domain in which voltage-dependent ionchannels are recruited. Overall, our results suggest a link between epigeneticregulation and axonal development in central neurons through a G9a-H3K9me2 ?dependent mechanism.