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

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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.
Alkuperäiskielienglanti
Artikkelie0214-17.2017
LehtieNeuro
Vuosikerta4
Numero5
Sivumäärä21
ISSN2373-2822
DOI - pysyväislinkit
TilaJulkaistu - 29 syyskuuta 2017
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 3112 Neurotieteet

Lainaa tätä

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title = "MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex",
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.",
keywords = "3112 Neurosciences",
author = "Kuan-Yin Tseng and Tatiana Danilova and Andrii Domanskyi and Mart Saarma and Lindahl, {Maria Susanna} and Airavaara, {Mikko Tuomas}",
year = "2017",
month = "9",
day = "29",
doi = "10.1523/ENEURO.0214-17.2017",
language = "English",
volume = "4",
journal = "eNeuro",
issn = "2373-2822",
publisher = "Society of Neuroscience",
number = "5",

}

MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex. / Tseng, Kuan-Yin; Danilova, Tatiana; Domanskyi, Andrii; Saarma, Mart; Lindahl, Maria Susanna; Airavaara, Mikko Tuomas.

julkaisussa: eNeuro, Vuosikerta 4, Nro 5, e0214-17.2017, 29.09.2017.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - MANF Is Essential for Neurite Extension and Neuronal Migration in the Developing Cortex

AU - Tseng, Kuan-Yin

AU - Danilova, Tatiana

AU - Domanskyi, Andrii

AU - Saarma, Mart

AU - Lindahl, Maria Susanna

AU - Airavaara, Mikko Tuomas

PY - 2017/9/29

Y1 - 2017/9/29

N2 - 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.

AB - 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.

KW - 3112 Neurosciences

UR - https://www.ncbi.nlm.nih.gov/pubmed/29082311

U2 - 10.1523/ENEURO.0214-17.2017

DO - 10.1523/ENEURO.0214-17.2017

M3 - Article

VL - 4

JO - eNeuro

JF - eNeuro

SN - 2373-2822

IS - 5

M1 - e0214-17.2017

ER -