However, DVL2−/− DVL3+/− and DVL1−/− DVL2−/− mice display much more severe NTD than DVL2−/− mice (Hamblet et al., 2002; Wang et al., 2006; Etheridge et al., 2008), which strongly suggests that DVL1 and DVL3 contribute directly or indirectly to neural tube closure. This evidence concerns the gene DVL3 and neural tube defect.