Essential Role of PDZ-RGS3 in the Maintenance of Neural Progenitor Cells

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Abstract
Ephrin‐B plays an important role in neural progenitor cells to regulate self‐renewal and differentiation. Cellular and embryological evidence suggest this function of ephrin‐B is mediated through a PDZ‐dependent reverse signaling mechanism. Here, we have genetically investigated the function of PDZ‐RGS3, a proposed downstream signaling mediator of ephrin‐B function, and found that knockout of PDZ‐RGS3 caused early cell cycle exit and precocious differentiation in neural progenitor cells of the developing cerebral cortex, reminiscent of the phenotype observed in ephrin‐B1 knockout mice. This resulted in a loss of cortical neural progenitor cells during cortical neurogenesis and led to impairment in the production of late born cortical neurons. These results reveal an essential role of PDZ‐RGS3 in maintaining the balance between self‐renewal and differentiation of neural progenitor cells and provide genetic evidence linking PDZ‐RGS3 to ephrin‐B reverse signaling. As ephrin‐B molecules are often differentially expressed in different types of neural progenitor/stem cells during development or in adult life, deletion of PDZ‐RGS3 can achieve a uniform loss of function of the ephrin‐B/regulator of G protein‐signaling (RGS) pathway, thereby providing a genetic tool useful for dissecting the mechanisms and functions of the ephrin‐B/RGS reverse signaling pathway in neural progenitor/stem cell regulation. STEM CELLS 2010; 28:1602–1610.
Funding Information
  • NIH (NS052388)