Zhang Xuying, Xiao Guanxi, Johnson Caroline, Cai Yuheng, Horowitz Zachary K, Mennicke Christine, Coffey Robert, Haider Mansoor, Threadgill David, Eliscu Rebecca, Oldham Michael C, Greenbaum Alon, Ghashghaei H Troy
Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA.
Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina at Chapel Hill, Raleigh, NC, USA.
iScience. 2023 Feb 20;26(3):106242. doi: 10.1016/j.isci.2023.106242. eCollection 2023 Mar 17.
The epidermal growth factor receptor (EGFR) plays a role in cell proliferation and differentiation during healthy development and tumor growth; however, its requirement for brain development remains unclear. Here we used a conditional mouse allele for to examine its contributions to perinatal forebrain development at the tissue level. Subtractive bulk ventral and dorsal forebrain deletions of uncovered significant and permanent decreases in oligodendrogenesis and myelination in the cortex and corpus callosum. Additionally, an increase in astrogenesis or reactive astrocytes in effected regions was evident in response to cortical scarring. Sparse deletion using mosaic analysis with double markers (MADM) surprisingly revealed a regional requirement for EGFR in rostrodorsal, but not ventrocaudal glial lineages including both astrocytes and oligodendrocytes. The EGFR-independent ventral glial progenitors may compensate for the missing EGFR-dependent dorsal glia in the bulk -deleted forebrain, potentially exposing a regenerative population of gliogenic progenitors in the mouse forebrain.
表皮生长因子受体(EGFR)在健康发育和肿瘤生长过程中的细胞增殖与分化中发挥作用;然而,其对脑发育的必要性仍不明确。在此,我们使用一种条件性小鼠等位基因来在组织水平上研究其对围产期前脑发育的贡献。对EGFR进行前脑腹侧和背侧的消减性整体缺失,发现皮质和胼胝体中的少突胶质细胞生成和髓鞘形成显著且永久性减少。此外,受影响区域的星形胶质细胞生成或反应性星形胶质细胞增加,这是对皮质瘢痕形成的反应。使用双标记镶嵌分析(MADM)进行的稀疏缺失令人惊讶地揭示,在包括星形胶质细胞和少突胶质细胞在内的吻背侧而非腹尾侧神经胶质谱系中,EGFR存在区域需求。不依赖EGFR的腹侧神经胶质祖细胞可能会补偿整体缺失前脑中缺失的依赖EGFR的背侧神经胶质,这可能揭示了小鼠前脑中神经胶质生成祖细胞的再生群体。