Formation of the vertebrate nervous system commences at neural induction, during which process na(i)ve ectodermal cells are specified along the epidermal or the neural cell fates.Inhibition of bone morphogenetic protein (BMP) signal is generally considered as a prerequisite for neural induction;however, it is unknown whether other signals are also involved in this process and how interference with rather than activation of a pathway is translated by the cells into a neural developmental program.Using the African clawed frog Xenopus laevis as a model system, our lab has previously shown that simultaneous inhibition of both activin/nodal and BMP signaling is crucial for neural induction to occur.Recently, our work further revealed that protein degradation is required for ectodermal cells to adopt a neural fate.The E3 ubiquitin ligases Smurf1 and2, Ectodermin, and-TrCP play different roles in neural induction, while several other E3 ubiquitin ligases, such as Siah2, Stub1, and ZNRF1, do not participate in neural induction.We showed that the stability of several transcription factors involved in activation of epidermal genes and/or inhibition of neural genes is regulated during the neural induction process.Ectopic expression of these transcription factors prevented neural induction in early Xenopus embryos.Our data thus suggest that TGF-signaling controls the expression and/or activities of a group of E3 ubiquitin ligases, which then influence early neural development through degradation of neural inhibitory transcription factors.