Asymmetric EGFR Alters Cell Fate

Abstract

Asymmetric distribution of signaling proteins is known to affect cell fate. Sun et al . determined that a subset of dividing cortical cells from the ventricular zone and subventricular zone of embryonic mice expressed epidermal growth factor receptor (EGFR) asymmetrically. Using three different assays, a subset of cultured cortical cells from embryonic day 13 to 17 (E13-17) mice produced daughter cells with asymmetric EGFR abundance such that one of the daughter cells received most of the EGFR. The frequency of asymmetry decreased with developmental stage. Daughter cells that received the most EGFR (EGFR high ) were more responsive to the proliferative effects of EGF, but both high and low EGFR cells responded similarly to fibroblast growth factor (FGF) and had similar abundance of the FGF receptor FGFR2. EGFR high cells also exhibited increased migratory activity relative to EGFR low cells when cultured in EGF-containing medium. Numb is known to be an asymmetrically distributed protein involved in cell fate specification. Although at early stages (E13), there was a correlation between Numb abundance and EGFR abundance, at later stages (E16-17) Numb distribution was symmetric between EGFR high and EGFR low cells. EGFR asymmetry was not dependent on Numb, because EGFR asymmetry was unaffected by loss of Numb and Numblike (based on analysis of cells from mutant mice). Asymmetric EGFR distribution was common in the progeny of cells that divided to form two progenitor cells and not in the progeny of cells that divided to form two neurons or one neuron and one progenitor cell. EGFR high cells acquired glial astrocyte markers and characteristics, whereas EGFR low cells have the capacity to become oligodendrocytes. Forced overexpression of EGFR resulted in the production of astrocytes at the expense of oligodendrocytes. Y. Sun, S. K. Goderie, S. Temple, Asymmetric distribution of EGFR receptor during mitosis generates diverse CNS progenitor cells. Neuron 45 , 873-886 (2005). [Online Journal]