Bulk and mosaic deletions of Egfr reveal regionally defined gliogenesis in the developing mouse forebrain.
Bulk and mosaic deletions of Egfr reveal regionally defined gliogenesis in the developing mouse forebrain.
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DOI：
10.1016/j.isci.2023.106242
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发表时间：
2023-03-17
期刊：
影响因子：
5.8
通讯作者：
Ghashghaei, H. Troy
中科院分区：
文献类型：
--
作者：
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
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 Egfr to examine its contributions to perinatal forebrain development at the tissue level. Subtractive bulk ventral and dorsal forebrain deletions of Egfr 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 Egfr-deleted forebrain, potentially exposing a regenerative population of gliogenic progenitors in the mouse forebrain. Bulk deletion of Egfr in the forebrain causes transient defects rostrally Bulk deletion of Egfr in the forebrain leads to defective OPC and myelination Sparse deletion of Egfr using MADM reveals its dosage effect on gliogenesis Sparse deletion of Egfr using MADM reveals its regional requirement for gliogenesis Neuroscience; Developmental neuroscience; Omics; Transcriptomics
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