NFIX regulates proliferation and migration within the murine SVZ neurogenic niche

Yee Hsieh Evelyn Heng, Bo Zhou, Lachlan Harris, Tracey Harvey, Aaron Smith, Elise Horne, Ben Martynoga, Jimena Andersen, Angeliki Achimastou, Kathleen Cato, Linda J. Richards, Richard M. Gronostajski, Giles S. Yeo, François Guillemot, Timothy L. Bailey, Michael Piper

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Transcription factors of the nuclear factor one (NFI) family play a pivotal role in the development of the nervous system. One member, NFIX, regulates the development of the neocortex, hippocampus, and cerebellum. Postnatal Nfix-/- mice also display abnormalities within the subventricular zone (SVZ) lining the lateral ventricles, a region of the brain comprising a neurogenic niche that provides ongoing neurogenesis throughout life. Specifically, Nfix-/- mice exhibit more PAX6-expressing progenitor cells within the SVZ. However, the mechanism underlying the development of this phenotype remains undefined. Here, we reveal that NFIX contributes to multiple facets of SVZ development. Postnatal Nfix-/- mice exhibit increased levels of proliferation within the SVZ, both in vivo and in vitro as assessed by a neurosphere assay. Furthermore, we show that the migration of SVZ-derived neuroblasts to the olfactory bulb is impaired, and that the olfactory bulbs of postnatal Nfix-/- mice are smaller.We also demonstrate that gliogenesis within the rostral migratory stream is delayed in the absence of Nfix, and reveal that Gdnf (glial-derived neurotrophic factor), a known attractant for SVZ-derived neuroblasts, is a target for transcriptional activation by NFIX. Collectively, these findings suggest that NFIX regulates both proliferation and migration during the development of the SVZ neurogenic niche.

Original languageEnglish
Pages (from-to)3758-3778
Number of pages21
JournalCerebral Cortex
Volume25
Issue number10
DOIs
StatePublished - Oct 2015

Keywords

  • Neuroblast
  • Nuclear factor one X
  • Olfactory bulb
  • Rostral migratory stream
  • Subventricular zone

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