Cnn3 regulates neural tube morphogenesis and neuronal stem cell properties.

Calponin 3 (Cnn3) is a member of the Cnn family of actin-binding molecules that is highly expressed in the mammalian brain and has been shown to control dendritic spine morphology, density, and plasticity by regulating actin cytoskeletal reorganization and dynamics. However, little is known about the role of Cnn3 during embryonic development. In this study, we analyzed mutant animals deficient in Cnn3 to gain a better understanding of its role in brain morphogenesis. Embryos lacking Cnn3 exhibited massive malformation of the developing brain including exoencephaly, closure defects at the rostral neural tube, and strong enlargement of brain tissue. In wild-type animals, we found Cnn3 being localized to the apical lining of the neuroepithelium in close vicinity to beta-Catenin and N-cadherin. By performing immunohistochemistry on beta-Catenin and p-Smad, and furthermore taking advantage of Wnt-reporter animals, we provide evidence that the loss of Cnn3 during development can affect signaling pathways crucial for correct morphogenesis of the neural tube. In addition, we used embryonic neurosphere cultures to investigate the role of Cnn3 in embryonic neuronal stem cells (NSC). Here, we observed that Cnn3 deficiency in NSCs increased the number of newly formed neurospheres and increased neurosphere size without perturbing their differentiation potential. Together, our study provides evidence for an important role of Cnn3 during development of the embryonic brain and in regulating NSC function.

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