Hnrpab regulates neural development and neuron cell survival after glutamate stimulation

John R. Sinnamon, Catherine B. Waddell, Sara Nik, Emily I. Chen, Kevin Czaplinski

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The molecular mechanisms that govern the timing and fate of neural stem-cell differentiation toward the distinct neural lineages of the nervous system are not well defined. The contribution of post-transcriptional regulation of gene expression to neural stem-cell maintenance and differentiation, in particular, remains inadequately characterized. The RNA-binding protein Hnrpab is highly expressed in developing nervous tissue and in neurogenic regions of the adult brain, but its role in neural development and function is unknown. We raised a mouse that lacks Hnrpab expression to define what role, if any, Hnrpab plays during mouse neural development. We performed a genome-wide quantitative analysis of protein expression within the hippocampus of newborn mice to demonstrate significantly altered gene expression in mice lacking Hnrpab relative to Hnrpab-expressing littermates. The proteins affected suggested an altered pattern of neural development and also unexpectedly indicated altered glutamate signaling. We demonstrate that Hnrpab -/- neural stem and progenitor cells undergo altered differentiation patterns in culture, and mature Hnrpab -/- neurons demonstrate increased sensitivity to glutamate-induced excitotoxicity. We also demonstrate that Hnrpab nucleocytoplasmic distribution in primary neurons is regulated by developmental stage. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)704-719
Number of pages16
JournalRNA
Volume18
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

Keywords

  • Mouse genetic knockout
  • Neural development
  • Neuron survival
  • RNA-binding proteins
  • Regulation of gene expression

ASJC Scopus subject areas

  • Molecular Biology

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