Before revision: The loss-of-function phenotype from Ecto mutant (C97A/C100A) , unable to perform ubiquitination, is similar to the phenotype present when Smad4 is over-expressed in the marginal zone, where neural markers show to be down-regulated .
After revision: In line with a RING-finger dependent ubiquitin-ligase activity of Ectodermin, an Ecto RING-finger mutant (C97A/C100A) , unable to perform ubiquitination, is similar to the phenotype present when Smad4 is inactive in gain-of-funtion .