title: 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.
authors.affiliation: Program in Neuroscience, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Sinnamon
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Waddell
authors.forename: Sara
authors.initials: S
authors.lastname: Nik
authors.forename: Emily I
authors.initials: EI
authors.lastname: Chen
authors.forename: Kevin
authors.initials: K
authors.lastname: Czaplinski
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018698:Glutamic Acid / Q000494:pharmacology*; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D012097:Repressor Proteins; C077048:Hnrnpab protein, mouse; D018698:Glutamic Acid