During gastrulation, ZEB2 (SIP1) is broadly expressed in the three germ layers, with the highest expression in the anterior neural fold, neural plate, then neural tube (inferred from mouse embryos). In human embryonic stem cells differentiated to neural cells, SOX2 binds about 6 kb upstream of the initiation codon of the ZEB2 gene (also called the SIP1 gene) and activates expression of ZEB2 (Chng et al. 2010). OCT4, NANOG, and SMAD2 also bind this region in ESCs and repress expression. However, OCT4, NANOG, and SMAD2 do not bind the ZEB2 gene during differentiation to neural tissue (Chng et al. 2010).