To ask if HDAC2 activity contributes to Notch loss-of-function phenotypes, we used the HDAC2 inhibitor Valproic acid (VPA) and discovered it could prevent the intestinal consequences of NDD and gamma secretase inhibitors (DBZ or DAPT) treatment in mice and spheroids, suggesting synergy between HDAC activity and pro-differentiation program in intestinal stem cells. Here, HDAC9 is linked to Neurodevelopmental delay.