ZNRF3 and microcephaly: Given that the activity of WDFY3 starts later than that of ZNRF3, it is likely that the WDFY3 missense variant that was associated with microcephaly and led to upregulation of Wnt/β-catenin signaling3 acts through excessive clonal expansion of apical progenitors but compromised neuronal differentiation as a plausible pathomechanism59 (Figure 6).