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Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density

Standard

Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density. / Middelkamp, Maximilian; Ruck, Lisa; Krisp, Christoph; Sumisławski, Piotr; Mohammadi, Behnam; Dottermusch, Matthias; Meister, Valerie; Küster, Lukas; Schlüter, Hartmut; Windhorst, Sabine; Neumann, Julia E.

in: ACTA NEUROPATHOL COM, Jahrgang 9, Nr. 1, 20.11.2021, S. 185.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Middelkamp, M, Ruck, L, Krisp, C, Sumisławski, P, Mohammadi, B, Dottermusch, M, Meister, V, Küster, L, Schlüter, H, Windhorst, S & Neumann, JE 2021, 'Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density', ACTA NEUROPATHOL COM, Jg. 9, Nr. 1, S. 185. https://doi.org/10.1186/s40478-021-01289-1

APA

Middelkamp, M., Ruck, L., Krisp, C., Sumisławski, P., Mohammadi, B., Dottermusch, M., Meister, V., Küster, L., Schlüter, H., Windhorst, S., & Neumann, J. E. (2021). Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density. ACTA NEUROPATHOL COM, 9(1), 185. https://doi.org/10.1186/s40478-021-01289-1

Vancouver

Middelkamp M, Ruck L, Krisp C, Sumisławski P, Mohammadi B, Dottermusch M et al. Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density. ACTA NEUROPATHOL COM. 2021 Nov 20;9(1):185. https://doi.org/10.1186/s40478-021-01289-1

Bibtex

@article{23fd584b1df34ea0af6ff91b04a46d24,
title = "Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density",
abstract = "LIN28A overexpression has been identified in malignant brain tumors called embryonal tumors with multilayered rosettes (ETMR) but its specific role during brain development remains largely unknown. Radial glia cells of the ventricular zone (VZ) are proposed as a cell of origin for ETMR. We asked whether an overexpression of LIN28A in such cells might affect brain development or result in the formation of brain tumors.Constitutive overexpression of LIN28A in hGFAP-cre::lsl-Lin28A (GL) mice led to a transient increase of proliferation in the cortical VZ at embryonic stages but no postnatal brain tumor formation. Postnatally, GL mice displayed a pyramidal cell layer dispersion of the hippocampus and altered spine and dendrite morphology, including reduced dendritic spine densities in the hippocampus and cortex. GL mice displayed hyperkinetic activity and differential quantitative MS-based proteomics revealed altered time dependent molecular functions regarding mRNA processing and spine morphogenesis. Phosphoproteomic analyses indicated a downregulation of mTOR pathway modulated proteins such as Map1b being involved in microtubule dynamics.In conclusion, we show that Lin28A overexpression transiently increases proliferation of neural precursor cells but it is not sufficient to drive brain tumors in vivo. In contrast, Lin28A impacts on protein abundancy patterns related to spine morphogenesis and phosphorylation levels of proteins involved in microtubule dynamics, resulting in decreased spine densities of neurons in the hippocampus and cortex as well as in altered behavior. Our work provides new insights into the role of LIN28A for neuronal morphogenesis and development and may reveal future targets for treatment of ETMR patients.",
author = "Maximilian Middelkamp and Lisa Ruck and Christoph Krisp and Piotr Sumis{\l}awski and Behnam Mohammadi and Matthias Dottermusch and Valerie Meister and Lukas K{\"u}ster and Hartmut Schl{\"u}ter and Sabine Windhorst and Neumann, {Julia E}",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
month = nov,
day = "20",
doi = "10.1186/s40478-021-01289-1",
language = "English",
volume = "9",
pages = "185",
journal = "ACTA NEUROPATHOL COM",
issn = "2051-5960",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density

AU - Middelkamp, Maximilian

AU - Ruck, Lisa

AU - Krisp, Christoph

AU - Sumisławski, Piotr

AU - Mohammadi, Behnam

AU - Dottermusch, Matthias

AU - Meister, Valerie

AU - Küster, Lukas

AU - Schlüter, Hartmut

AU - Windhorst, Sabine

AU - Neumann, Julia E

N1 - © 2021. The Author(s).

PY - 2021/11/20

Y1 - 2021/11/20

N2 - LIN28A overexpression has been identified in malignant brain tumors called embryonal tumors with multilayered rosettes (ETMR) but its specific role during brain development remains largely unknown. Radial glia cells of the ventricular zone (VZ) are proposed as a cell of origin for ETMR. We asked whether an overexpression of LIN28A in such cells might affect brain development or result in the formation of brain tumors.Constitutive overexpression of LIN28A in hGFAP-cre::lsl-Lin28A (GL) mice led to a transient increase of proliferation in the cortical VZ at embryonic stages but no postnatal brain tumor formation. Postnatally, GL mice displayed a pyramidal cell layer dispersion of the hippocampus and altered spine and dendrite morphology, including reduced dendritic spine densities in the hippocampus and cortex. GL mice displayed hyperkinetic activity and differential quantitative MS-based proteomics revealed altered time dependent molecular functions regarding mRNA processing and spine morphogenesis. Phosphoproteomic analyses indicated a downregulation of mTOR pathway modulated proteins such as Map1b being involved in microtubule dynamics.In conclusion, we show that Lin28A overexpression transiently increases proliferation of neural precursor cells but it is not sufficient to drive brain tumors in vivo. In contrast, Lin28A impacts on protein abundancy patterns related to spine morphogenesis and phosphorylation levels of proteins involved in microtubule dynamics, resulting in decreased spine densities of neurons in the hippocampus and cortex as well as in altered behavior. Our work provides new insights into the role of LIN28A for neuronal morphogenesis and development and may reveal future targets for treatment of ETMR patients.

AB - LIN28A overexpression has been identified in malignant brain tumors called embryonal tumors with multilayered rosettes (ETMR) but its specific role during brain development remains largely unknown. Radial glia cells of the ventricular zone (VZ) are proposed as a cell of origin for ETMR. We asked whether an overexpression of LIN28A in such cells might affect brain development or result in the formation of brain tumors.Constitutive overexpression of LIN28A in hGFAP-cre::lsl-Lin28A (GL) mice led to a transient increase of proliferation in the cortical VZ at embryonic stages but no postnatal brain tumor formation. Postnatally, GL mice displayed a pyramidal cell layer dispersion of the hippocampus and altered spine and dendrite morphology, including reduced dendritic spine densities in the hippocampus and cortex. GL mice displayed hyperkinetic activity and differential quantitative MS-based proteomics revealed altered time dependent molecular functions regarding mRNA processing and spine morphogenesis. Phosphoproteomic analyses indicated a downregulation of mTOR pathway modulated proteins such as Map1b being involved in microtubule dynamics.In conclusion, we show that Lin28A overexpression transiently increases proliferation of neural precursor cells but it is not sufficient to drive brain tumors in vivo. In contrast, Lin28A impacts on protein abundancy patterns related to spine morphogenesis and phosphorylation levels of proteins involved in microtubule dynamics, resulting in decreased spine densities of neurons in the hippocampus and cortex as well as in altered behavior. Our work provides new insights into the role of LIN28A for neuronal morphogenesis and development and may reveal future targets for treatment of ETMR patients.

U2 - 10.1186/s40478-021-01289-1

DO - 10.1186/s40478-021-01289-1

M3 - SCORING: Journal article

C2 - 34801069

VL - 9

SP - 185

JO - ACTA NEUROPATHOL COM

JF - ACTA NEUROPATHOL COM

SN - 2051-5960

IS - 1

ER -