MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex

ENeuro
Kuan-Yin TsengMikko Airavaara

Abstract

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) resident protein with neuroprotective effects. Previous studies have shown that MANF expression is altered in the developing rodent cortex in a spatiotemporal manner. However, the role of MANF in mammalian neurogenesis is not known. The aim of this study was to determine the role of MANF in neural stem cell (NSC) proliferation, differentiation, and cerebral cortex development. We found that MANF is highly expressed in neural lineage cells, including NSCs in the developing brain. We discovered that MANF-deficient NSCs in culture are viable and show no defect in proliferation. However, MANF-deficient cells have deficits in neurite extension upon neuronal differentiation. In vivo, MANF removal leads to slower neuronal migration and impaired neurite outgrowth. In vitro, mechanistic studies indicate that impaired neurite growth is preceded by reduced de novo protein synthesis and constitutively activated unfolded protein response (UPR) pathways. This study is the first to demonstrate that MANF is a novel and critical regulator of neurite growth and neuronal migration in mammalian cortical development.

Citations

Mar 24, 2018·Journal of Neurochemistry·Ana UzquianoFiona Francis
Jul 10, 2019·Molecular & Cellular Proteomics : MCP·Filip HumenikMichel Salzet
Dec 18, 2018·Frontiers in Physiology·Su YangXiao-Jiang Li
Dec 6, 2018·Frontiers in Physiology·Pedro Sousa-VictorJoana Neves
Aug 28, 2020·Cell and Tissue Research·Maria Jӓntti, Brandon K Harvey
Sep 1, 2019·Molecular & Cellular Proteomics : MCP·Filip HumenikMichel Salzet
Jun 28, 2018·Trends in Neurosciences·Gabriela MartínezClaudio Hetz
Oct 17, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Yi YangYuxian Shen
Apr 24, 2021·Journal of Biomedical Science·Nan SunJinquan Cai
May 18, 2021·Frontiers in Aging Neuroscience·Xue-Chun LiuGui-Hai Chen

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Datasets Mentioned

BETA
AB5622

Methods Mentioned

BETA
light microscopy
protein folding

Software Mentioned

ImageJ
Image Pro Plus
Cell Life Science Microscopy
GraphPad Prism
Image Studio

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