SFPQ associates to LSD1 and regulates the migration of newborn pyramidal neurons in the developing cerebral cortex

Int J Dev Neurosci. 2017 Apr:57:1-11. doi: 10.1016/j.ijdevneu.2016.12.006. Epub 2016 Dec 26.

Abstract

The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex.

Keywords: Corticogenesis; Epigenetic regulation; Neuronal migration.

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Cell Line
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cerebral Cortex* / cytology
  • Cerebral Cortex* / embryology
  • Cerebral Cortex* / growth & development
  • Doublecortin Domain Proteins
  • Electroporation
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Homeodomain Proteins / metabolism
  • Ki-67 Antigen / metabolism
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Neuropeptides / metabolism
  • Nuclear Proteins / metabolism
  • PTB-Associated Splicing Factor / genetics
  • PTB-Associated Splicing Factor / metabolism*
  • Pyramidal Cells / physiology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / metabolism
  • SOXB1 Transcription Factors / metabolism

Substances

  • Cux1 protein, mouse
  • Doublecortin Domain Proteins
  • Homeodomain Proteins
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Nuclear Proteins
  • PTB-Associated Splicing Factor
  • RNA, Small Interfering
  • Repressor Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Histone Demethylases
  • KDM1a protein, mouse