Hnrpab regulates neural development and neuron cell survival after glutamate stimulation

RNA. 2012 Apr;18(4):704-19. doi: 10.1261/rna.030742.111. Epub 2012 Feb 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Glutamic Acid / pharmacology*
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / physiology*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Mice
  • Mice, Knockout
  • Neurons / cytology*
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*


  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Repressor Proteins
  • Hnrnpab protein, mouse
  • Glutamic Acid