Fig. 3.

YAP-Notch signaling cross talk promotes Paneth cell differentiation and intestinal stem cell niche reestablishment. At the onset of the culture, intestinal stem cells lose the Lgr5 expression and have uniform YAP (blue) nuclear localization. Variability in YAP cellular localization occurs with organoid growth and when a critical cell number is reached, the first Paneth cell emerges and expresses lysozyme (Lyz) and the Notch ligand delta-like 1 (Dll1) which activates the Notch1 (N1) receptor on neighboring cells. These cells lose YAP nuclear localization and re-express Lgr5, making them competent to receive Wnt signals from Paneth cells. Lgr5 re-expressing cells express Hes1: a readout for active Notch signaling, which may contribute to Notch lateral inhibition with the neighboring Paneth cell forming a negative feedback loop to maintain its identity