Our study points to several surprising differences in human versus mouse forebrain development such as human-specific expression of FOXA2 in hESC derived ventral forebrain progenitors and in CS15 human forebrain tissue. We speculate that transient FOXA2 expression reflects a prolonged requirement for SHH signaling during human development given the obvious differences in brain size and extended proliferation of SHH dependent progenitors. To further address this hypothesis, it will be important to establish a time course of FOXA2 expression during human ventral forebrain development and to determine whether FOXA2 is linked to SHH expression as commonly observed in other FOXA2+ CNS domains such as the floor plate (Placzek and Briscoe, 2005).
