In response to WNT signaling, CTNNB1 (beta-catenin) binds upstream of the GBX2 transcription start site and activates expression in a way that requires TCF binding sites (inferred from Xenopus homologs in Li et al. 2009). This may be the event that initiates GBX2 expression in the neural plate border region. Both TFAP2A and TFAP2B bind the GBX2 locus 4.2 kb downstream of the transcription start site, and GBX2 expression is downregulated in TFAP2B knockdown experiments. This suggests that the TFAP2A:TFAP2B heterodimer binds the GBX2 gene and increases expression (inferred from chicken homologs in Rothstein and Simoes-Costa 2020). TFAP2A is expressed after GBX2 in human cells (Leung et al. 2016) so TFAP2A:TFAP2B may maintain rather than initiate expression of GBX2..