Hnrpab regulates neural development and neuron cell survival after glutamate stimulation

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.