RBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury

Xinzhou Zhu (), Jingyi Yan, Catherine Bregere, Andrea Zelmer, Tessa Goerne, Josef P. Kapfhammer, Raphael Guzman and Sven Wellmann ()
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Xinzhou Zhu: University Children’s Hospital Basel (UKBB), University of Basel
Jingyi Yan: University Children’s Hospital Basel (UKBB), University of Basel
Catherine Bregere: University of Basel
Andrea Zelmer: University Children’s Hospital Basel (UKBB), University of Basel
Tessa Goerne: University Children’s Hospital Basel (UKBB), University of Basel
Josef P. Kapfhammer: University of Basel
Raphael Guzman: University of Basel
Sven Wellmann: University Children’s Hospital Basel (UKBB), University of Basel

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Hypoxic ischemia (HI) is an acute brain threat across all age groups. Therapeutic hypothermia ameliorates resulting injury in neonates but its side effects prevent routine use in adults. Hypothermia up-regulates a small protein subset that includes RNA-binding motif protein 3 (RBM3), which is neuroprotective under stressful conditions. Here we show how RBM3 stimulates neuronal differentiation and inhibits HI-induced apoptosis in the two areas of persistent adult neurogenesis, the subventricular zone (SVZ) and the subgranular zone (SGZ), while promoting neural stem/progenitor cell (NSPC) proliferation after HI injury only in the SGZ. RBM3 interacts with IGF2 mRNA binding protein 2 (IMP2), elevates its expression and thereby stimulates IGF2 release in SGZ but not SVZ-NSPCs. In summary, we describe niche-dependent regulation of neurogenesis after adult HI injury via the novel RBM3-IMP2-IGF2 signaling pathway.

Date: 2019
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DOI: 10.1038/s41467-019-11870-x

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