Dmrt5 controls corticotrope and gonadotrope differentiation in the zebrafish pituitary

Dmrt transcription factors control sex determination or sex-specific differentiation across all invertebrate and vertebrate species, where they have been studied so far. Besides important functions in the reproductive system, also non-gonadal roles have been assigned to several dmrt family members. One example is dmrt5 that was shown to guide neurogenesis in the forebrain of some vertebrates including fish. Here we show that in zebrafish, dmrt5 is also expressed adjacent to the pituitary anlage and later in the anterior pars distalis (aPD) where it organizes differentiation of endocrine cells. We find that pituitary induction, cell survival, proliferation and early lineage specification in the pituitary is independent of dmrt5. Instead, dmrt5 is required for terminal differentiation of corticotropes and gonadotropes. Gene knock-down and mutant analysis revealed that dmrt5 promotes corticotrope differentiation via tbx19 expression while it prevents gonadotrope differentiation in the aPD. In dmrt5 morphants and mutants, reduced corticotrope numbers may result in irregular positioning and reduced maintenance of lactotropes. In conclusion, our study establishes a novel function for dmrt5 for cell differentiation in the anterior pituitary. Intriguingly, its effect on gonadotrope numbers defines a first non-gonadal role for a dmrt family member that appears crucial for the activity of the reproductive system.