Asymmetric Distribution of EGFR Receptor during Mitosis Generates Diverse CNS Progenitor Cells

It has been debated whether asymmetric distribution of cell surface receptors during mitosis could generate asymmetric cell divisions by yielding daughters with different environmental responsiveness and, thus, different fates. We have found that in mouse embryonic forebrain ventricular and subventricular zones, the EGFR can distribute asymmetrically during mitosis in vivo and in vitro. This occurs during divisions yielding two Nestin+ progenitor cells, via an actin-dependent mechanism. The resulting sibling progenitor cells respond differently to EGFR ligand in terms of migration and proliferation. Moreover, they express different phenotypic markers: the EGFRhigh daughter usually has radial glial/astrocytic markers, while its EGFRlow sister lacks them, indicating fate divergence. Lineage trees of cultured cortical glioblasts reveal repeated EGFR asymmetric distribution, and asymmetric divisions underlie formation of oligodendrocytes and astrocytes in clones. These data suggest that asymmetric EGFR distribution contributes to forebrain development by creating progenitors with different proliferative, migratory, and differentiation responses to ligand.