Loss of LGL1 increases expression of c-Jun and DCX in the SVZ and RMS of the mouse brain

Author

Madison Leigh Gutierrez, Humboldt State UniversityFollow

Graduation Date

Fall 2025

Document Type

Thesis

Program

Master of Science degree with a major in Biology

Committee Chair Name

Amy Sprowles

Committee Chair Affiliation

Cal Poly Humboldt Faculty or Staff

Second Committee Member Name

Brigitte Blackman

Second Committee Member Affiliation

Cal Poly Humboldt Faculty or Staff

Third Committee Member Name

Karen Kiemnec-Tyburczy

Third Committee Member Affiliation

Cal Poly Humboldt Faculty or Staff

Keywords

Brain, DCX, C-JUN, GBM, Glioblastoma

Subject Categories

Biology

Abstract

Glioblastoma (GBM), the most aggressive and treatment-resistant subtype of glioma, accounts for the majority of brain tumor–related mortality. A defining feature of GBM is its ability to invade healthy brain tissue through extensive cell migration, which severely limits the effectiveness of surgical and pharmacological treatments. Increasing evidence suggests that GBM cells activate gene programs known to drive normal neural stem and progenitor cell (NSPC) migration; however, the precise molecular mechanisms shared between NSPCs and GBM cells remain poorly understood. Lethal (2) giant larvae 1 (Lgl1), a conserved cortical cytoskeletal protein, has emerged as a key regulator of polarity and migration. Its loss disrupts NSPC migration while simultaneously promoting migratory behaviors in GBM cells. This study investigates how conditional loss of Lgl1 in glial fibrillary acid protein (GFAP) expressing neural stem cells in the adult subventricular zone alters the expression of migration-associated proteins. Specifically, I focused on two proteins linked to NSPC and GBM motility: the AP-1 transcription factor subunit c-Jun and the microtubule-associated protein Doublecortin (DCX). I utilized coronal sections from tamoxifen-induced p42 GFAP- GFAP Cre^ERT2; Lgl1^fl/fl;^CAG-tdTom+/+ and GFAP-Cre^ERT2; Lgl1^{+/+; CAG-tdTom tdTom+/+} mice to compare c-Jun and DCX expression patterns in in the subventricular zone (SVZ) and rostral migratory stream (RMS) after LGL1 deletion in GFAP-expressing neural stem cells. Immunofluorescent analysis revealed that loss of Lgl1 leads to increased expression of both c-Jun and DCX in these regions. To further probe the regulatory relationship between c-Jun and DCX, I employed the UCSC Genome Browser and identified predicted c-Jun binding sites within both the Homo sapiens and Mus musculus Dcx gene orthologs. These findings suggest that transcriptional regulation of DCX by c-Jun may contribute to the altered migratory phenotype we observed in Lgl1-deficient NSPCs in vitro. Future studies investigating how Lgl1 loss influences cytoskeletal dynamics and transcriptional regulation through factors like c-Jun and DCX will be valuable for identifying novel therapeutic targets to reduce the invasive capacity of GBM cells.

Citation Style

APA 7

Recommended Citation

Gutierrez, Madison Leigh, "Loss of LGL1 increases expression of c-Jun and DCX in the SVZ and RMS of the mouse brain" (2025). Cal Poly Humboldt theses and projects. 2528.
https://digitalcommons.humboldt.edu/etd/2528