α-Klotho regulates mouse embryonic neural stem cell proliferation and differentiation.
Abstract
A longevity factor α-Klotho has been shown to be neuroprotective and enhance brain function. However, it has not been elucidated whether α-Klotho is involved in the embryonic brain development. To address this, we investigated whether α-Klotho regulates embryonic neural stem cell proliferation and differentiation. We found that α-Klotho is expressed in the mouse embryonic brain and neural stem cells isolated from the embryonic day 13.5 brains. When α-Klotho was knocked down in the embryonic neural stem cells, basal level of apoptosis increased while proliferation decreased. Overexpression of membrane-bound or secreted form of α-Klotho promoted proliferation of the mouse embryonic neural stem cells. Knockdown of α-Klotho suppressed the phosphorylation of Akt and ERK, suggesting that α-Klotho may promote neural stem cell survival and proliferation by activating signaling pathway involving Akt and ERK. In addition, knockdown of α-Klotho suppressed differentiation of embryonic neural stem cells into neurons or oligodendrocytes but not astrocytes. These results suggest that α-Klotho may have a role in neuronal development by promoting neural stem cell survival, proliferation and differentiation.
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Research summary
The paper investigates the role of α-Klotho in embryonic neural stem cell proliferation and differentiation, which is relevant to understanding mechanisms that may influence brain development and potentially longevity. However, the findings are primarily focused on developmental biology rather than directly addressing aging or lifespan extension. The impact is limited as it provides solid research but does not significantly advance the field of longevity research.
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