title: Dmrt5 controls corticotrope and gonadotrope differentiation in the zebrafish pituitary.
abstract: Dmrt transcription factors control sex determination or sex-specific differentiation across all invertebrate and vertebrate species, in which they have been studied so far. In addition to important functions in the reproductive system, also nongonadal roles have been assigned to several dmrt family members. One example is dmrt5, which 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 in which 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 knockdown and mutant analysis revealed that dmrt5 promotes corticotrope differentiation via tbx19 expression, whereas it prevents gonadotrope differentiation in the anterior pars distalis. 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 nongonadal role for a dmrt family member that appears crucial for the activity of the reproductive system.
authors.affiliation: Department of Biological Sciences and Centre for Bioimaging Sciences, National University of Singapore, Singapore 117543.
authors.forename: Martin
authors.initials: M
authors.lastname: Graf
authors.forename: Elizabeth-Raye
authors.initials: ER
authors.lastname: Teo Qi-Wen
authors.forename: Menachem Viktor
authors.initials: MV
authors.lastname: Sarusie
authors.forename: Flora
authors.initials: F
authors.lastname: Rajaei
authors.forename: Christoph
authors.initials: C
authors.lastname: Winkler
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D019070:Cell Lineage; D052680:Corticotrophs / Q000166:cytology* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D052681:Gonadotrophs / Q000166:cytology* / Q000378:metabolism*; D007031:Hypothalamus / Q000196:embryology; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C493902:Dmrta2 protein, zebrafish; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins