Bulk and mosaic deletions of Egfr reveal regionally defined gliogenesis in the developing mouse forebrain

Egfr 的大片段和嵌合缺失揭示了发育中小鼠前脑中区域性定义的胶质细胞生成

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作者:Xuying Zhang ,Guanxi Xiao ,Caroline Johnson ,Yuheng Cai ,Zachary K Horowitz ,Christine Mennicke ,Robert Coffey ,Mansoor Haider ,David Threadgill ,Rebecca Eliscu ,Michael C Oldham ,Alon Greenbaum ,H Troy Ghashghaei

Abstract

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. Keywords: Developmental neuroscience; Neuroscience; Omics; Transcriptomics.

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