In zebrafish intestines Dll1 homologue is also highly expressed in secretory cells, and its inhibition leads to secretory cell expansion. Notch signalling is unidirectional and it is mediated by Deltaexpressing cells sending a signal and Notch-expressing cells receiving it. In Drosophila, Delta/Notch signalling involves repression of Delta in Notch-expressing cells. Thus, Liensinine-Perchlorate the absence of Delta ligand in developinggoblet or Panethcells can providea ‘‘signal receiving’’ role instead of ‘‘signal sending’’, which in turn can increase Hes5 expression in them. PAR1 is known to be important for Delta ligand localisation in Drosophila, so we speculate that the failure in MARK activation in the absence of Lkb1 may directly lead to the lack of Delta ligand in Lkb1 deficient Paneth and goblet cells and subsequent deregulation of secretory cell differentiation. The regulation of secretory cell fate by the Notch pathway is dependent on whether the cell is proliferative or post-mitotic. In proliferative cells,Rebaudioside-D Notch and Hes1 repress a conversion of all dividing crypt cells into goblet cells and this conversion occurs if Notch is inhibited. Conversely, a very brief induction of Notch pathway drives the differentiation of post-mitotic cells into mature goblet cells via Hes5 expression. In our studies, we did not observe changes in overall Hes1 levels, but Hes5 levels were notably higher, suggesting that Lkb1 deletion is more important for the differentiation at the post-mitotic stage. The failure in secretory cell terminal differentiation after Lkb1 deletion resembled the effects observed after the terminal differentiation of cell precursors into Paneth cells was blocked via SV40 T antigen expression. This also led to the substitution of the mature Paneth cells with intermediate Paneth/goblet cells showing a decrease in the granule’s electrondense core diameter and expansion of the mucinous area. Notch signalling misregulation observed in Lkb1-deficient intestines may also be explained by consequences arising from the altered terminal differentiation of Paneth cells development. Clearly, further studies are required to address this possibility.