Two C. elegans DM domain proteins, DMD-3 and MAB-3, function in late stages of male somatic gonad development

• Published in: Developmental biology 2024-10, Vol.514, p.50-65
• Main Authors: Smith, Michele, Lesperance, Megan, Herrmann, Alyssa, Vernooy, Stephanie, Cherian, Asher, Kivlehan, Emily, Whipple, Lauren, Portman, Douglas S., Mason, D. Adam
• Format: Article
• Language: English
• Subjects: adulthood; ancestry; cell death; cell movement; DM domain; domain; genes; hindgut; hormone receptors; Linker cell; males; metalloproteinases; Morphogenesis; mutants; sex determination; Sexual differentiation; Sexual dimorphism; Somatic gonad; transcription factors; zinc
• ISSN: 0012-1606; 1095-564X; 1095-564X
• DOI: 10.1016/j.ydbio.2024.06.008

To bring about sexual dimorphism in form, information from the sex determination pathway must trigger sex-specific modifications in developmental programs. DM-domain encoding genes have been found to be involved in sex determination in a multitude of animals, often at the level of male somatic gonad formation. Here we report our findings that the DM-domain transcription factors MAB-3 and DMD-3 function together in multiple steps during the late stages of C. elegans male somatic gonad development. Both mab-3 and dmd-3 are expressed in the linker cell and hindgut of L4 males and dmd-3 is also expressed in presumptive vas deferens cells. Furthermore, dmd-3, but not mab-3, expression in the linker cell is downstream of nhr-67, a nuclear hormone receptor that was previously shown to control late stages of linker cell migration. In mab-3; dmd-3 double mutant males, the last stage of linker cell migration is partially defective, resulting in aberrant linker cell shapes and often a failure of the linker cell to complete its migration to the hindgut. When mab-3; dmd-3 double mutant linker cells do complete their migration, they fail to be engulfed by the hindgut, indicating that dmd-3 and mab-3 activity are essential for this process. Furthermore, linker cell death and clearance are delayed in mab-3; dmd-3 double mutants, resulting in the linker cell persisting into adulthood. Finally, DMD-3 and MAB-3 function to activate expression of the bZIP transcription factor encoding gene zip-5 and downregulate the expression of the zinc metalloprotease ZMP-1 in the linker cell. Taken together, these results demonstrate a requirement for DM-domain transcription factors in controlling C. elegans male gonad formation, supporting the notion that the earliest DM-domain genes were involved in male somatic gonad development in the last common ancestor of the bilaterians. [Display omitted] •Two C. elegans DM domain transcription factor encoding genes, mab-3 and dmd-3, are expressed in multiple tissues involved in male somatic gonad development.•mab-3; dmd-3 double mutants display defects in linker cell migration, resulting in aberrant linker cell morphology and premature arrest in many double mutant males.•mab-3; dmd-3 double mutants also display defects in linker cell engulfment by the hindgut and subsequent linker cell death and clearance.•MAB-3 and DMD-3 partially inhibit expression of the zinc matrix metalloproteinase encoding gene zmp-1 and activate expression of a basic leuci