Abstract
Selfish genetic elements that act as post-segregation distorters cause lethality in non-carrier individuals after fertilization. Two post-segregation distorters have been previously identified in Caenorhabditis elegans, the peel-1/zeel-1 and the sup-35/pha-1 elements. These elements seem to act as modification-rescue systems, also called toxin/antidote pairs. Here we show that the maternal-effect toxin/zygotic antidote pair sup-35/pha-1 is required for proper expression of apical junction (AJ) components in epithelia and that sup-35 toxicity increases when pathways that establish and maintain basal epithelial characteristics, die-1, elt-1, lin-26, and vab-10, are compromised. We demonstrate that pha-1(e2123) embryos, which lack the antidote, are defective in epidermal morphogenesis and frequently fail to elongate. Moreover, seam cells are frequently misshaped and mispositioned and cell bond tension is reduced in pha-1(e2123) embryos, suggesting altered tissue material properties in the epidermis. Several aspects of this phenotype can also be induced in wild-type embryos by exerting mechanical stress through uniaxial loading. Seam cell shape, tissue mechanics, and elongation can be restored in pha-1(e2123) embryos if expression of the AJ molecule DLG-1/Discs large is reduced. Thus, our experiments suggest that maternal-effect toxicity disrupts proper development of the epidermis which involves distinct transcriptional regulators and AJ components.
Highlights
In search for embryonic lethal mutations, developmental geneticists have uncovered numerous organ master regulators and terminal differentiation factors in the nematode Caenorhabditis elegans, the arthropod Drosophila melanogaster, or the chordate Danio rerio
Observations of presumptive epidermal malformation in pha1(e2123) led to the assumption that PHA-1 might have a broader role in C. elegans embryonic development (Kuzmanov et al, 2014)
Our experiments demonstrate that PHA-1 seems to be involved in epidermal morphogenesis by attenuating the toxic effect of SUP-35 (Figure 1)
Summary
In search for embryonic lethal mutations, developmental geneticists have uncovered numerous organ master regulators and terminal differentiation factors in the nematode Caenorhabditis elegans, the arthropod Drosophila melanogaster, or the chordate Danio rerio. The DAC contains the membrane-associated guanylate cyclase (MAGUK) scaffold protein DLG-1 (Discs large in Drosophila) and the nematode-specific AJ component AJM-1 This complex, together with LET-413 (Scribble in Drosophila), serves as a polarization cue for the distribution of apical and basolateral factors and divides the epithelial membrane into distinct functional zones (similar to tight junctions in mammals). We uncover that by laser cutting dorsoventral cell–cell contacts, a significant reversal of elongation can be induced in WT embryos, most likely due to the previously described stiffness anisotropy in the dorsal epidermis (Vuong-Brender et al, 2017) and force anisotropy (recently reviewed in Carvalho and Broday, 2020) This elastic response is completely lost in pha-1(e2123) embryos and can be recovered by reduced expression of the AJ component DLG-1 or by creating mechanical stress through uniaxial loading, pointing to overall altered tissue biomechanics. We provide evidence that these phenomena, altered spatiotemporal expression of AJ components, altered cell bond, and tissue mechanics are most likely resulting in the terminal phenotypes described previously
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