Figure 5 from FOXR2 Targets LHX6⁺/DLX⁺ Neural Lineages to Drive Central Nervous System Neuroblastoma

Foxr2 is oncogenic in the ventral telencephalon in mice. A, Schematic describing the IUE-based strategy to model FOXR2-driven brain tumors. PiggyBac and CRISPR vectors are delivered into neural stem cells in the GEs at E12.5. After birth, mice develop tumors and are euthanized when neurologic symptoms become apparent. B, Representative brightfield (BF) and fluorescence (GFP) images of a GFP+ Foxr2-driven tumor (top, whole brain; bottom, coronal section). C, Kaplan–Meier survival curves of tumor-bearing mice carrying Foxr2 overexpression alone (Foxr2 alone, n = 6) or in combination with p53 LOF (Foxr2 p53^LOF, n = 6). Statistical comparisons using the log-rank Mantel–Cox test are described in Supplementary Table S1. D, Immunofluorescence of Foxr2 alone tissue in coronal sections from the striatum. Lesions driven by Foxr2 overexpression alone are GFP+ and colocalize with V5. Cells harboring Foxr2 overexpression alone possess low levels of Ki67 and Olig2. However, cells in these lesions are positive for NeuN, DCX, and GFAP. Scale bar, 50 μm. E, IHC detection of hematoxylin and eosin (H&E), GFP, and Ki67 in coronal forebrain sections from Foxr2 p53^LOF tumor-bearing symptomatic mice. Tumor cells are GFP+. Scale bars, 1 mm in the low-magnification panels and 100 μm in the high-magnification panels. F, Immunofluorescence for GFP, Foxr2-V5, Ki67, Olig2, NeuN, DCX, and GFAP in coronal forebrain sections from Foxr2 p53^LOF tumor-bearing symptomatic mice. Cells within the tumor in the striatum are GFP+, colocalize with V5, and many are actively proliferating, as indicated by the presence of Ki67. Individual tumor cells are also positive for Olig2, NeuN, DCX, and GFAP. Scale bar, 50 μm.