The Regulation and Function of Soxb1 Genes and Proteins during Neural Induction

In Xenopus laevis, ectodermal cells are induced to form neural tissue when BMP signaling is inhibited. Little is known about the steps following inhibition of BMP that allows for the expression of early neural genes such as sox2, sox3 and geminin. This research investigates the regulation and function of the SoxB1 genes and proteins which are activated by BMP inhibition during neural induction in Xenopus. We use gain and loss of function assays to determine that BMP signaling inhibits the expression of the soxB1 gene, sox3 via its downstream targets, XVent1 and XVent2. Additionally, we demonstrate that FGF signaling is required for the induction of sox2, but is only required for the maintenance of sox3 and geminin. Our data indicates that although the same signals and factors are involved in the expression and repression of early neural genes, there is no common neurogenic code regulating neural induction in Xenopus laevis. Moreover, since the soxB1 genes are expressed at the onset of neural induction and are required for normal neural development, we analyze their role in neural induction and formation. We demonstrate that overexpression of Sox2 and Sox3 directly activates expression of the neural progenitor marker, geminin, thereby expanding the neural tube and delaying neuronal differentiation. This progenitor expansion occurs at the expense of epidermis and neural crest formation indicating that the SoxB1 proteins are involved in the fate choice between epidermis and neural tissue and they act to promote neurogenesis at the expense of non-neural ectodermal derivatives.