To test the assumption that HDAC2 activity contributes to Notch loss-of-function phenotypes we used the broad acting HDAC2 inhibitor Valproic acid (VPA) and discovered it could block the intestinal consequences of NDD as well as gamma secretase inhibitor treatment (DBZ or DAPT) in mice and spheroids, respectively, suggesting synergy between HDAC activity and pro-differentiation program in intestinal stem cells. This evidence concerns the gene HDAC2 and Neurodevelopmental delay.