GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma

Area of Science:

• * Neuro-oncology
• * Molecular biology
• * Developmental biology

Background:

• * Glioma-associated oncogene homolog 3 (GLI3) is known to inhibit GLI1 and is implicated in neuronal differentiation.
• * The specific molecular subtypes of medulloblastoma exhibiting increased GLI3 expression remain unclear.

Purpose of the Study:

• * To investigate the expression patterns of GLI3 across different medulloblastoma molecular subtypes.
• * To elucidate the role of GLI3 in neuronal differentiation and morphology within WNT- and SHH-activated medulloblastoma.

Main Methods:

• * Immunohistochemistry was performed on two independent cohorts (total 88 cases) to assess GLI3 protein levels.
• * Bulk mRNA expression data and single-cell RNA sequencing were analyzed to confirm gene expression.
• * Localization of GLI3, GLI1, and GLI2 was examined in relation to specific cellular areas within tumor subtypes.

Main Results:

• * GLI3 expression was found to be high in both WNT- and SHH-activated medulloblastoma subtypes.
• * Both GLI1 and GLI3 were highly expressed in SHH-activated medulloblastoma, while only GLI3 was highly expressed in WNT-activated medulloblastoma.
• * GLI3 showed distinct localization patterns: within neuronal nodules in SHH-medulloblastoma and diffusely in WNT-medulloblastoma, contrasting with GLI1/2 expression patterns.

Conclusions:

• * GLI3 is significantly expressed in both WNT- and SHH-activated medulloblastoma.
• * The findings suggest GLI3 plays a crucial role as a potential master regulator of neuronal differentiation and morphology in these medulloblastoma subgroups.