hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation

Judith Niesen; Irm Hermans-Borgmeyer; Christina Krüger; Melanie Schoof; Franziska Modemann; Ulrich Schüller

doi:10.1016/j.isci.2023.107501

hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation

Standard

hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation. / Niesen, Judith; Hermans-Borgmeyer, Irm; Krüger, Christina ; Schoof, Melanie ; Modemann, Franziska ; Schüller, Ulrich.

in: ISCIENCE, Jahrgang 26, Nr. 9, 15.09.2023, S. 107501.

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

Harvard

Niesen, J, Hermans-Borgmeyer, I, Krüger, C , Schoof, M , Modemann, F & Schüller, U 2023, 'hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation', ISCIENCE, Jg. 26, Nr. 9, S. 107501. https://doi.org/10.1016/j.isci.2023.107501

APA

Niesen, J., Hermans-Borgmeyer, I., Krüger, C., Schoof, M., Modemann, F., & Schüller, U. (2023). hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation. ISCIENCE, 26(9), 107501. https://doi.org/10.1016/j.isci.2023.107501

Vancouver

Niesen J, Hermans-Borgmeyer I, Krüger C , Schoof M , Modemann F , Schüller U. hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation. ISCIENCE. 2023 Sep 15;26(9):107501. https://doi.org/10.1016/j.isci.2023.107501

Bibtex

@article{d59808cc5eda4af091e5071a28e01ed5,

title = "hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation",

abstract = "The zinc-finger transcription factor GLI2 is frequently amplified in childhood medulloblastoma of the Sonic-hedgehog type (SHH-MB), with or without amplification of NMYC or deletion of TP53. Despite the aggressive tumor behavior, tumorigenesis is not well understood, and adequate mouse models are lacking. Therefore, we generated mice with a GLI2 overexpression under control of the hGFAP-promoter. These mice died within 150 days. The majority only survived until postnatal day 40. They displayed severe cerebellar hypoplasia, cortical malformations, but no brain tumors, except for one out of 23 animals with an undifferentiated hindbrain lesion. Additional loss of p53 did not result in cerebellar tumors, but partially rescued the cerebellar phenotype induced by GLI2 overexpression. Similarly, the combination of GLI2 and NMYC was neither sufficient for the development of SHH-MB. We therefore assume that the development of childhood SHH-MB in mice is either occurring in cellular origins outside the hGFAP-positive lineage or needs additional genetic drivers.",

author = "Judith Niesen and Irm Hermans-Borgmeyer and Christina Kr{\"u}ger and Melanie Schoof and Franziska Modemann and Ulrich Sch{\"u}ller",

note = "{\textcopyright} 2023 The Author(s).",

year = "2023",

month = sep,

day = "15",

doi = "10.1016/j.isci.2023.107501",

language = "English",

volume = "26",

pages = "107501",

journal = "ISCIENCE",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "9",

}

RIS

TY - JOUR

T1 - hGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation

AU - Niesen, Judith

AU - Hermans-Borgmeyer, Irm

AU - Krüger, Christina

AU - Schoof, Melanie

AU - Modemann, Franziska

AU - Schüller, Ulrich

PY - 2023/9/15

Y1 - 2023/9/15

N2 - The zinc-finger transcription factor GLI2 is frequently amplified in childhood medulloblastoma of the Sonic-hedgehog type (SHH-MB), with or without amplification of NMYC or deletion of TP53. Despite the aggressive tumor behavior, tumorigenesis is not well understood, and adequate mouse models are lacking. Therefore, we generated mice with a GLI2 overexpression under control of the hGFAP-promoter. These mice died within 150 days. The majority only survived until postnatal day 40. They displayed severe cerebellar hypoplasia, cortical malformations, but no brain tumors, except for one out of 23 animals with an undifferentiated hindbrain lesion. Additional loss of p53 did not result in cerebellar tumors, but partially rescued the cerebellar phenotype induced by GLI2 overexpression. Similarly, the combination of GLI2 and NMYC was neither sufficient for the development of SHH-MB. We therefore assume that the development of childhood SHH-MB in mice is either occurring in cellular origins outside the hGFAP-positive lineage or needs additional genetic drivers.

AB - The zinc-finger transcription factor GLI2 is frequently amplified in childhood medulloblastoma of the Sonic-hedgehog type (SHH-MB), with or without amplification of NMYC or deletion of TP53. Despite the aggressive tumor behavior, tumorigenesis is not well understood, and adequate mouse models are lacking. Therefore, we generated mice with a GLI2 overexpression under control of the hGFAP-promoter. These mice died within 150 days. The majority only survived until postnatal day 40. They displayed severe cerebellar hypoplasia, cortical malformations, but no brain tumors, except for one out of 23 animals with an undifferentiated hindbrain lesion. Additional loss of p53 did not result in cerebellar tumors, but partially rescued the cerebellar phenotype induced by GLI2 overexpression. Similarly, the combination of GLI2 and NMYC was neither sufficient for the development of SHH-MB. We therefore assume that the development of childhood SHH-MB in mice is either occurring in cellular origins outside the hGFAP-positive lineage or needs additional genetic drivers.

U2 - 10.1016/j.isci.2023.107501

DO - 10.1016/j.isci.2023.107501

M3 - SCORING: Journal article

C2 - 37608807

VL - 26

SP - 107501

JO - ISCIENCE

JF - ISCIENCE

SN - 2589-0042

IS - 9

ER -