Essential role of PDZ-RGS3 in the maintenance of neural progenitor cells.
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.
Qiu
Runxiang
R
Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
Wang
Jun
J
Tsark
Walter
W
Lu
Qiang
Q
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D036387:Ephrin-B1 / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D020710:RGS Proteins; D015398:Signal Transduction; D013997:Time Factors
C092571:Efnb1 protein, mouse; D036387:Ephrin-B1; D020690:GTPase-Activating Proteins; D020710:RGS Proteins; C415085:Rgs3 protein, mouse; D019204:GTP-Binding Proteins