Research ExplorerPublicationsCo-activation of Sonic hedgehog and Wnt signaling in murine ...

Co-activation of Sonic hedgehog and Wnt signaling in murine retinal precursor cells drives ocular lesions with features of intraocular medulloepithelioma

Standard

Co-activation of Sonic hedgehog and Wnt signaling in murine retinal precursor cells drives ocular lesions with features of intraocular medulloepithelioma. / Dottermusch, Matthias; Sumisławski, Piotr; Krevet, Julia; Middelkamp, Maximilian; Voß, Hannah; Siebels, Bente; Bartsch, Harald; Sotlar, Karl; Meyer, Peter; Frank, Stephan; Korshunov, Andrey; Glatzel, Markus; Schüller, Ulrich; Neumann, Julia E.

In: ONCOGENESIS, Vol. 10, No. 11, 16.11.2021, p. 78.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Dottermusch, M, Sumisławski, P, Krevet, J, Middelkamp, M, Voß, H, Siebels, B, Bartsch, H, Sotlar, K, Meyer, P, Frank, S, Korshunov, A, Glatzel, M, Schüller, U & Neumann, JE 2021, 'Co-activation of Sonic hedgehog and Wnt signaling in murine retinal precursor cells drives ocular lesions with features of intraocular medulloepithelioma', ONCOGENESIS, vol. 10, no. 11, pp. 78. https://doi.org/10.1038/s41389-021-00369-0

APA

Dottermusch, M., Sumisławski, P., Krevet, J., Middelkamp, M., Voß, H., Siebels, B., Bartsch, H., Sotlar, K., Meyer, P., Frank, S., Korshunov, A., Glatzel, M., Schüller, U., & Neumann, J. E. (2021). Co-activation of Sonic hedgehog and Wnt signaling in murine retinal precursor cells drives ocular lesions with features of intraocular medulloepithelioma. ONCOGENESIS, 10(11), 78. https://doi.org/10.1038/s41389-021-00369-0

Vancouver

Dottermusch M, Sumisławski P, Krevet J, Middelkamp M, Voß H, Siebels B et al. Co-activation of Sonic hedgehog and Wnt signaling in murine retinal precursor cells drives ocular lesions with features of intraocular medulloepithelioma. ONCOGENESIS. 2021 Nov 16;10(11):78. https://doi.org/10.1038/s41389-021-00369-0

Bibtex

@article{382a911377a74333bc71c868a232556a,
title = "Co-activation of Sonic hedgehog and Wnt signaling in murine retinal precursor cells drives ocular lesions with features of intraocular medulloepithelioma",
abstract = "Intraocular medulloepithelioma (IO-MEPL) is a rare embryonal ocular neoplasm, prevalently occurring in children. IO-MEPLs share histomorphological features with CNS embryonal tumors with multilayered rosettes (ETMRs), referred to as intracranial medulloepitheliomas. While Sonic hedgehog (SHH) and WNT signaling pathways are crucial for ETMR pathogenesis, the impact of these pathways on human IO-MEPL development is unclear. Gene expression analyses of human embryonal tumor samples revealed similar gene expression patterns and significant overrepresentation of SHH and WNT target genes in both IO-MEPL and ETMR. In order to unravel the function of Shh and Wnt signaling for IO-MEPL pathogenesis in vivo, both pathways were activated in retinal precursor cells in a time point specific manner. Shh and Wnt co-activation in early Sox2- or Rax-expressing precursor cells resulted in infiltrative ocular lesions that displayed extraretinal expansion. Histomorphological, immunohistochemical, and molecular features showed a strong concordance with human IO-MEPL. We demonstrate a relevant role of WNT and SHH signaling in IO-MEPL and report the first mouse model to generate tumor-like lesions with features of IO-MEPL. The presented data may be fundamental for comprehending IO-MEPL initiation and developing targeted therapeutic approaches.",
author = "Matthias Dottermusch and Piotr Sumis{\l}awski and Julia Krevet and Maximilian Middelkamp and Hannah Vo{\ss} and Bente Siebels and Harald Bartsch and Karl Sotlar and Peter Meyer and Stephan Frank and Andrey Korshunov and Markus Glatzel and Ulrich Sch{\"u}ller and Neumann, {Julia E}",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
month = nov,
day = "16",
doi = "10.1038/s41389-021-00369-0",
language = "English",
volume = "10",
pages = "78",
journal = "ONCOGENESIS",
issn = "2157-9024",
publisher = "NATURE PUBLISHING GROUP",
number = "11",

}

RIS

TY - JOUR

T1 - Co-activation of Sonic hedgehog and Wnt signaling in murine retinal precursor cells drives ocular lesions with features of intraocular medulloepithelioma

AU - Dottermusch, Matthias

AU - Sumisławski, Piotr

AU - Krevet, Julia

AU - Middelkamp, Maximilian

AU - Voß, Hannah

AU - Siebels, Bente

AU - Bartsch, Harald

AU - Sotlar, Karl

AU - Meyer, Peter

AU - Frank, Stephan

AU - Korshunov, Andrey

AU - Glatzel, Markus

AU - Schüller, Ulrich

AU - Neumann, Julia E

N1 - © 2021. The Author(s).

PY - 2021/11/16

Y1 - 2021/11/16

N2 - Intraocular medulloepithelioma (IO-MEPL) is a rare embryonal ocular neoplasm, prevalently occurring in children. IO-MEPLs share histomorphological features with CNS embryonal tumors with multilayered rosettes (ETMRs), referred to as intracranial medulloepitheliomas. While Sonic hedgehog (SHH) and WNT signaling pathways are crucial for ETMR pathogenesis, the impact of these pathways on human IO-MEPL development is unclear. Gene expression analyses of human embryonal tumor samples revealed similar gene expression patterns and significant overrepresentation of SHH and WNT target genes in both IO-MEPL and ETMR. In order to unravel the function of Shh and Wnt signaling for IO-MEPL pathogenesis in vivo, both pathways were activated in retinal precursor cells in a time point specific manner. Shh and Wnt co-activation in early Sox2- or Rax-expressing precursor cells resulted in infiltrative ocular lesions that displayed extraretinal expansion. Histomorphological, immunohistochemical, and molecular features showed a strong concordance with human IO-MEPL. We demonstrate a relevant role of WNT and SHH signaling in IO-MEPL and report the first mouse model to generate tumor-like lesions with features of IO-MEPL. The presented data may be fundamental for comprehending IO-MEPL initiation and developing targeted therapeutic approaches.

AB - Intraocular medulloepithelioma (IO-MEPL) is a rare embryonal ocular neoplasm, prevalently occurring in children. IO-MEPLs share histomorphological features with CNS embryonal tumors with multilayered rosettes (ETMRs), referred to as intracranial medulloepitheliomas. While Sonic hedgehog (SHH) and WNT signaling pathways are crucial for ETMR pathogenesis, the impact of these pathways on human IO-MEPL development is unclear. Gene expression analyses of human embryonal tumor samples revealed similar gene expression patterns and significant overrepresentation of SHH and WNT target genes in both IO-MEPL and ETMR. In order to unravel the function of Shh and Wnt signaling for IO-MEPL pathogenesis in vivo, both pathways were activated in retinal precursor cells in a time point specific manner. Shh and Wnt co-activation in early Sox2- or Rax-expressing precursor cells resulted in infiltrative ocular lesions that displayed extraretinal expansion. Histomorphological, immunohistochemical, and molecular features showed a strong concordance with human IO-MEPL. We demonstrate a relevant role of WNT and SHH signaling in IO-MEPL and report the first mouse model to generate tumor-like lesions with features of IO-MEPL. The presented data may be fundamental for comprehending IO-MEPL initiation and developing targeted therapeutic approaches.

U2 - 10.1038/s41389-021-00369-0

DO - 10.1038/s41389-021-00369-0

M3 - SCORING: Journal article

C2 - 34785636

VL - 10

SP - 78

JO - ONCOGENESIS

JF - ONCOGENESIS

SN - 2157-9024

IS - 11

ER -