Bulk and Mosaic Deletions of Egfr Reveal Regionally Defined Gliogenesis in the Developing Mouse Forebrain

Abstract

The Epidermal growth factor receptor (EGFR) plays a role in cell proliferation and differentiation in healthy development and in tumors, 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 deletions of Egfr revealed that ventral but not dorsal telencephalic EGFR expression is critical for forebrain homeostasis and the presence of transiently EGFR-dependent glial lineages including robust depletion of oligodendrocytes that last the mouse’s lifetime. Sparse deletion using Mosaic Analysis with Double Markers (MADM) surprisingly reveals a regional requirement for EGFR in dorsal, but not ventral glial lineages including both astrocytes and oligodendrocytes. These findings lead to a model in which EGFR-independent ventral glial progenitors compensate for the absence of EGFR-dependent dorsal glia in the forebrain, thus masking its precise role in the bulk model.

Funding Information: National Institutes of Health grant R01NS098370 and R01NS089795 (HTG).

Declaration of Interests: Authors declare that they have no competing interests.

Ethics Approval Statement: Mice were used under the regulations and approval from Institutional Animal Care and Use Committee and at North Carolina State University.

Keywords: EGFR, Stem cells, gliogenesis, Neurogenesis, progenitor, Oligodendrocytes, astrocytes, Myelination, White matter, Cerebral Cortex, MADM, mouse, forebrain