TY - JOUR
T1 - Hnrpab regulates neural development and neuron cell survival after glutamate stimulation
AU - Sinnamon, John R.
AU - Waddell, Catherine B.
AU - Nik, Sara
AU - Chen, Emily I.
AU - Czaplinski, Kevin
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - Mouse genetic knockout
KW - Neural development
KW - Neuron survival
KW - RNA-binding proteins
KW - Regulation of gene expression
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U2 - 10.1261/rna.030742.111
DO - 10.1261/rna.030742.111
M3 - Article
C2 - 22332140
AN - SCOPUS:84858676050
SN - 1355-8382
VL - 18
SP - 704
EP - 719
JO - RNA
JF - RNA
IS - 4
ER -