For example, moderately altered levels of Noggin, as observed in Chd1Δ2/Δ2 ESCs, may be buffered in vivo e.g. by increased BMP levels or by compensatory induction of other remodeling factors, such as the closely related Chd2 that shares biochemical features with Chd1 and was shown to cause developmental delay in a gene-trap mouse model51, 52, whereas such compensatory pathways may be restricted in the artificial cell culture environment. Here, NOG is linked to Global developmental delay.