Drosophila hamlet mediates epithelial tissue assembly of the reproductive system

Epithelial tissue fusion requires coordinated molecular events at the ends of two epithelial structures. Regulatory mechanisms controlling these events remain largely elusive. In the Drosophila reproductive system (RS), this fusion unites the gonad and the genital disc-derived tissues, into a contin...

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Main Authors: Huazhen Wang, Ludivine Bertonnier-Brouty, Isabella Artner, Jiayu Wen, Qi Dai
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-07-01
Series:eLife
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Online Access:https://elifesciences.org/articles/104164
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author Huazhen Wang
Ludivine Bertonnier-Brouty
Isabella Artner
Jiayu Wen
Qi Dai
author_facet Huazhen Wang
Ludivine Bertonnier-Brouty
Isabella Artner
Jiayu Wen
Qi Dai
author_sort Huazhen Wang
collection DOAJ
description Epithelial tissue fusion requires coordinated molecular events at the ends of two epithelial structures. Regulatory mechanisms controlling these events remain largely elusive. In the Drosophila reproductive system (RS), this fusion unites the gonad and the genital disc-derived tissues, into a continuous tube. This study unveils the pivotal role of Hamlet (Ham), a Drosophila PR domain containing transcription factor, in orchestrating epithelial tissue fusion in the RS. Loss of ham leads to sterility and disconnection between the testes and seminal vesicles. Systematic analysis of Ham downstream genes reveals cytoskeletal, metabolic regulators and signaling pathway components. Ham activates genes for epithelial differentiation and remodeling, while repressing genes required for tissue growth and patterning. Using multiplexed in situ hybridization, we demonstrate spatial–temporal gene expression dynamics in contacting epithelia. Key Ham downstream effectors include E-Cadherin (E-Cad), Toll (Tl), and Wnt2 signaling pathways, regulating tissue interaction and fusion. Our findings present a comprehensive gene network crucial for heterotypic epithelial tissue fusion. Mammalian Ham orthologs PRDM3 and PRDM16 are highly expressed in epithelial tissues, suggesting a conserved role across species.
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spelling doaj-art-811fdb4e951142bea9d6edb8944f50cc2025-08-20T03:31:30ZengeLife Sciences Publications LtdeLife2050-084X2025-07-011310.7554/eLife.104164Drosophila hamlet mediates epithelial tissue assembly of the reproductive systemHuazhen Wang0https://orcid.org/0000-0002-4875-1829Ludivine Bertonnier-Brouty1https://orcid.org/0000-0003-1294-3244Isabella Artner2https://orcid.org/0000-0002-2895-5664Jiayu Wen3https://orcid.org/0000-0003-1249-6456Qi Dai4https://orcid.org/0000-0002-2082-0693Department of Molecular Bioscience, the Wenner-Gren Institute, Stockholm University, Stockholm, SwedenLund University, Lund, Sweden; Lund University Diabetes Center, Lund University, Malmö, SwedenLund University, Lund, Sweden; Lund University Diabetes Center, Lund University, Malmö, SwedenDivision of Genome Sciences and Cancer, The John Curtin School of Medical Research, The Australian National University, and Australian Research Council Centre of Excellence for the Mathematical Analysis of Cellular Systems, Canberra, AustraliaDepartment of Molecular Bioscience, the Wenner-Gren Institute, Stockholm University, Stockholm, SwedenEpithelial tissue fusion requires coordinated molecular events at the ends of two epithelial structures. Regulatory mechanisms controlling these events remain largely elusive. In the Drosophila reproductive system (RS), this fusion unites the gonad and the genital disc-derived tissues, into a continuous tube. This study unveils the pivotal role of Hamlet (Ham), a Drosophila PR domain containing transcription factor, in orchestrating epithelial tissue fusion in the RS. Loss of ham leads to sterility and disconnection between the testes and seminal vesicles. Systematic analysis of Ham downstream genes reveals cytoskeletal, metabolic regulators and signaling pathway components. Ham activates genes for epithelial differentiation and remodeling, while repressing genes required for tissue growth and patterning. Using multiplexed in situ hybridization, we demonstrate spatial–temporal gene expression dynamics in contacting epithelia. Key Ham downstream effectors include E-Cadherin (E-Cad), Toll (Tl), and Wnt2 signaling pathways, regulating tissue interaction and fusion. Our findings present a comprehensive gene network crucial for heterotypic epithelial tissue fusion. Mammalian Ham orthologs PRDM3 and PRDM16 are highly expressed in epithelial tissues, suggesting a conserved role across species.https://elifesciences.org/articles/104164hamletPRDM factorsthe reproductive systemepithelial tissue fusiongene network
spellingShingle Huazhen Wang
Ludivine Bertonnier-Brouty
Isabella Artner
Jiayu Wen
Qi Dai
Drosophila hamlet mediates epithelial tissue assembly of the reproductive system
eLife
hamlet
PRDM factors
the reproductive system
epithelial tissue fusion
gene network
title Drosophila hamlet mediates epithelial tissue assembly of the reproductive system
title_full Drosophila hamlet mediates epithelial tissue assembly of the reproductive system
title_fullStr Drosophila hamlet mediates epithelial tissue assembly of the reproductive system
title_full_unstemmed Drosophila hamlet mediates epithelial tissue assembly of the reproductive system
title_short Drosophila hamlet mediates epithelial tissue assembly of the reproductive system
title_sort drosophila hamlet mediates epithelial tissue assembly of the reproductive system
topic hamlet
PRDM factors
the reproductive system
epithelial tissue fusion
gene network
url https://elifesciences.org/articles/104164
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AT isabellaartner drosophilahamletmediatesepithelialtissueassemblyofthereproductivesystem
AT jiayuwen drosophilahamletmediatesepithelialtissueassemblyofthereproductivesystem
AT qidai drosophilahamletmediatesepithelialtissueassemblyofthereproductivesystem