Role of Mammalian Formin Fhod3 in Neural Tube Closure

抄録

Apical constriction is the process in which contraction of the apical F-actin network causes the cell to take on a wedged shape. Neural tube closure requires apical constriction to facilitate folding process of neural plate into neural tube. We have previously generated knockout mice lacking Fhod3, a member of formin family proteins that mediate nucleation and polymerization of F-actin. Fhod3 null embryos died around E11.5 because of defects in cardiac development, but also showed defects in neural tube closure, suggesting that Fhod3 is involved in apical constriction in neural tube closure. However, the mechanism of action is poorly understood. Here we investigated the role of Fhod3 in neurulation using Fhod3^{-/-Tg(α-MHC-Fhod3)}embryos in which cardiac defects were rescued by transgenic expression of Fhod3 in the heart but the neural tube failed to close because of the absence of Fhod3 in the neural tube. The rescued Fhod3^{-/-Tg(α-MHC-Fhod3)}embryos appear normal up to E8.0, but show a failure of neural tube closure from the hindbrain/cervical boundary towards rostral portion. Consistent with this, LacZ staining showed that Fhod3 begins to be expressed around E8.0 in hindbrain especially at the dorsolateral neural plate. At hindbrain level, the apical accumulation of F-actin and myosin heavy chain was disturbed in Fhod3 null embryos. These data indicate that Fhod3 regulates apical constriction in neural tube closure by mediating apical F-actin contraction.