[en] The bHLH transcription factors belonging to the ARP/Ascl superfamily are key regulators of cell differentiation in a wide range of tissues. We noticed a striking diversity among these ARP/Ascl factors when involved in the determination and differentiation of the endocrine cells. In this study, we first assessed whether different members of the ARP/Ascl family could rescue the gut phenotype of the ascl1a-/- zebrafish mutant, that presents a loss of all intestinal secretory cells. We showed that Neurod1 is the only factor of the family able to rescue the enteroendocrine cells while the others only rescue goblet cells in ascl1a-/- mutant intestine, and highlighted that this role is modulated by an Evolutionary Conserved Domain (ECD) in the protein. Additionally, RNA-sequencing analysis suggest that ECD domain acts as a repressor of the goblet lineage. Furthermore, we investigated the role of ECD domain within the endogenous gene by creating a zebrafish mutant line by CRISPR/Cas9 and performed loss of function studies. Finally, we introduced insights on interacting partners of Neurod1. Altogether, the results of our study provide new understanding in Neurod1 mechanism of action, especially through the highlight of a conserved domain present after the bHLH domain that seems important for target gene repression.
