The formation of functional organs requires the coordinated integration of distinct epithelial tissues. A central challenge in this process is how heterotypic epithelial populations recognize one another, remodel their properties, and establish stable structural and luminal continuity. Despite its fundamental importance during organogenesis, the molecular mechanisms governing heterotypic epithelial tissue fusion remain poorly understood. In this thesis, I use the male reproductive system (RS) as a model to investigate the transcriptional regulation of epithelial tissue remodeling and fusion, with a particular focus on the PRDI-BF1–RIZ1 (PR)-domain transcription factors Hamlet (Ham) and PRDM16. By combining studies in Drosophila melanogaster and mouse, I examine how these factors guide epithelial morphogenesis and assess whether their functions are evolutionarily conserved. 

In the first paper, I identify a previously unrecognized role for Ham in epithelial remodeling and fusion between the testis and seminal vesicle of the Drosophila male reproductive tract. Ham is required for the specification of testis terminal epithelial cells, as complete loss of ham results in the absence of this cell population. Furthermore, even a modest reduction of Ham levels disrupts epithelial tube fusion. Transcriptomic and genetic analyses reveal that Ham regulates an extensive gene network involved in epithelial differentiation, cell adhesion, cytoskeletal organization and signaling. Ham activates genes required for epithelial differentiation and remodeling while repressing genes associated with tissue growth and patterning. Key downstream effectors include E-cadherin, Toll, and Wnt2 signaling pathways, which together coordinate epithelial interactions and tissue fusion. These findings define a comprehensive gene regulatory network underlying heterotypic epithelial tissue fusion.

 Given the evolutionary conservation of Ham and its orthologs, and the remarkable sensitivity of the RS to reduced Ham activity, I next investigate the function of PRDM16 in the murine reproductive tract. In the second paper, I show that PRDM16 is specifically expressed in a subset of somatic gonadal precursor cells and their descendant rete testis (RT) epithelial cells. Loss of Prdm16 leads to defective RT morphogenesis, characterized by reduced cell proliferation, decreased E-cadherin expression and impaired lumen formation. These defects are accompanied by disrupted WNT and BMP signaling, suggesting that PRDM16 coordinates signaling, and transcriptional programs required for epithelial tissue organization.

Together, these findings uncover an evolutionarily conserved role for Ham and PRDM16 in epithelial morphogenesis and tissue connectivity. They establish a comparative framework for understanding how transcriptional programs regulate epithelial tissue fusion during organogenesis.