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The Histone Methyltransferase G9a Controls Axon Growth by Targeting the RhoA Signaling Pathway.

Carlos Wilson1, Luciana E Giono2, Victoria Rozés-Salvador3

  • 1Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET-UNC) Friuli 2434, 5016 Córdoba, Argentina; Universidad Nacional de Córdoba (UNC), Av. Haya de la Torre s/n, 5000 Córdoba, Argentina; Centro de Investigación en Medicina Traslacional "Severo R Amuchástegui" (CIMETSA), Instituto Universitario Ciencias Biomédicas Córdoba (IUCBC), Av. Friuli 2786, 5016 Córdoba, Argentina.

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|May 14, 2020
PubMed
Summary
This summary is machine-generated.

Histone methyltransferase G9a regulates neuronal polarity by controlling axon formation. Its inhibition increases RhoA-ROCK activity, hindering neuronal development and migration.

Keywords:
G9aH3K9me2LfcRhoAaxondevelopmentepigeneticshistone methyltransferaseneuronspolarity

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Epigenetics

Background:

  • Axon and dendrite formation are crucial for brain circuitry and function.
  • The RhoA-Rho kinase (ROCK) pathway inhibits axon development.
  • Genetic regulation of neuronal polarity is not well understood.

Purpose of the Study:

  • To investigate the role of histone methyltransferase G9a in neuronal polarity.
  • To explore the molecular mechanisms by which G9a influences neuronal development.

Main Methods:

  • Primary neuron cultures were used to study gene expression and protein localization.
  • RNA interference (RNAi) and pharmacological inhibition were employed to suppress G9a function.
  • Neuronal migration, axon initiation, and polarity establishment were assessed in situ and in vitro.
  • Expression levels of RhoA, ROCK, and the guanine nucleotide exchange factor Lfc were analyzed.

Main Results:

  • G9a and its isoform G9a/E10+ expression peaked during axon formation in primary neurons.
  • Suppression of G9a/E10+ or G9a activity impaired neuronal migration, axon initiation, and polarity.
  • G9a inhibition led to increased RhoA-ROCK pathway activity.
  • This increase was mediated by elevated expression of Lfc, a RhoA-specific GEF.

Conclusions:

  • G9a plays a significant role in establishing neuronal polarity.
  • G9a regulates neuronal polarity partly through the RhoA-ROCK signaling pathway.
  • G9a acts upstream of Lfc to modulate RhoA activity during neuronal development.