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Hence, Dobreva et al. (2006) have found that Satb2 represses the expression of several Hox genes, including Hoxa2. This gene encodes an inhibitor of bone formation and regulator of branchial arch patterning. According to Konopka et al. (2009) HOX2A is among FOXP2��s targets. Also, the phenotype linked to chromosome 2q32-q33 deletions and to the haploinsufficiency of SATB2 can be mimicked by the haploinsufficiency of GTF3C3, a gene that is also a target of FOXP2 (Konopka et al., 2009). In the context of Satb2, we wish to point out that a strong Gli3 binding region is located just over 100 kb �� of Satb2 in neural tissue (Vokes et al., 2007). Gli3 interacts with Shh during thalamic development (this website Haddad-T��volli et al., 2012). Moreover, Gli3 regulates calvarial suture development by controlling Bmp-Smad signaling, which integrates a Dlx5/Runx2-II cascade (Tanimoto et al., 2012). Actually, mutations in GLI3 have been found in people affected by Greig cephalopolysyndactyly syndrome, a condition in which craniosynostosis is an important feature (Debeer et al., 2003). Interestingly, most (?98%) of Altaic Neanderthals and Denisovans had a different sequence in GLI3 compared to AMHs: while the latter retained the ancestral sequence, the former gained a non-synonymous change that appears to be mildly disruptive (Castellano et al., 2014). Given the role of Satb2 in the establishment of callosal projections, it is also interesting that Gli3 controls corpus callosum formation by positioning midline guideposts during telencephalic patterning (Magnani et al., 2014), altering expressions of Slit1/2, Fgf8, and Wnt/��-catenin, genes we discussed at length in Boeckx and Ben��tez-Burraco (2014a). ZBTB20 At this point we would like to briefly mention another gene, ZBTB20, which also shows signs of selection in AMHs (Green et al., 2010). We find this gene of interest because it defines a hippocampal neuronal identity through direct repression of genes that control projection neuron development in the isocortex, among which we found Fezf2, Satb2, Tbr1, and Foxp2 (Nielsen et al., 2014). In addition, although we do not know of any direct evidence for an interaction between ZBTB20 and RUNX2 in the hippocampus, we note that Kuhlwilm et al. (2013) found several genes of the ZBTB family to be differentially expressed after RUNX2 transfection in neuroblastomic SH-SY5Y cells. PAX6 Although we are not aware of any signal of positive selection of PAX6 in AMHs, there are robust links between them and RUNX2, FOXP2, AUTS2, and other genes discussed above. PAX6 encodes a transcription factor involved in the development of the eye and the brain. Although perhaps best known as the master regulator or master selector of eye development (Gehring and Ikeo, 1999), in the brain it affects the process of glutamatergic neuron differentiation (Kim et al., 2014).