The WNT/β-catenin pathway genes, including WNT7B, are specifically enriched in the deep layers and subplate in the human embryonic cortex during the late second trimester (Abu-Khalil et al., 2004; Miller et al., 2014).
WNT/β-catenin signaling regulates the specification of subplate neurons into deep-layer neurons by suppressing callosal projection fate and promoting the alternative subcortical projection fate in a layer-specific manner (Ozair et al., 2018).
Similar to its localization in vivo, WNT7B was enriched in the deep CP layers of SNOs and progressively established mutually exclusive domains with the SATB2+ upper layers from day 100 to day 150 (Figure 5A). Notably, the deep-layer-specific enrichment of WNT7B was already apparent at day 100, preceding the establishment of separated cortical layers, suggesting that WNT7B expression could regulate but is not the result of cortical layer specification