Wolbachia action in the sperm produces developmentally deferred chromosome segregation defects during the Drosophila mid-blastula transition

Abstract

Wolbachia, a vertically transmitted endosymbiont infecting many insects, spreads rapidly through uninfected populations by a mechanism known as cytoplasmic incompatibility (CI). In CI, a paternally delivered modification of the sperm leads to chromatin defects and lethality during and after the first mitosis of embryonic development in multiple species. However, whether CI-induced defects in later stage embryos are a consequence of the first division errors or caused by independent defects remains unresolved. To address this question, we focused on ~1/3 of embryos from CI crosses in Drosophila simulans that develop apparently normally through the first and subsequent pre-blastoderm divisions before exhibiting mitotic errors during the mid-blastula transition and gastrulation. We performed single embryo PCR and whole genome sequencing to find a large percentage of these developed CI-derived embryos bypass the first division defect. Using fluorescence in situ hybridization, we find increased chromosome segregation errors in gastrulating CI-derived embryos that had avoided the first division defect. Thus, Wolbachia action in the sperm induces developmentally deferred defects that are not a consequence of the first division errors. Like the immediate defect, the delayed defect is rescued through crosses to infected females. These studies inform current models on the molecular and cellular basis of CI.

Prophage proteins alter long noncoding RNA and DNA of developing sperm to induce a paternal-effect lethality

“…4, A and D). In some embryos at the same stage, we observed chromatin-bridging defects colocalized with DNA damage signals and arrested chromatids at the metaphase as shown earlier ( 41 ) (Fig. 4, B).…”

“…4, B), indicative of a distinct effect with which CI associates throughout development. This DNA damage may precipitate the recent observation of nuclear fallout in the peripheral cells of CI embryos ( 41 ). We propose that late CI embryos (2 to 3 hours AED) that escape the first mitotic defect accumulate fatal damage through successive nuclear divisions, leading to mortality.…”

“…Previous studies showed that Drosophila embryonic DNA damage is only evident in late stages of development ~6 hours after egg deposition (AED) toward gastrulation (33)(34)(35), as the cells at this stage become hyperprolifertive, and hence, more susceptible to damage (36)(37)(38). Although CI is often associated with a first-mitotic division defect within 1 hour of egg fertilization, additional developmental defects also occur in late CI embryos developing through the preblastoderm divisions, syncytial, and cellularized blastoderms (10,(39)(40)(41). We collected embryos aged 0 to 1 hour, 1 to 2 hours, and 2 to 3 hours AED from CI, non-CI, and rescue crosses.…”

The mechanism of cytoplasmic incompatibility is conserved in Wolbachia-infected Aedes aegypti mosquitoes deployed for arbovirus control

“…Once fertilization occurs, the canonical cellular consequences of CI are delayed paternal chromatin condensation, paternal chromatin bridges, and segregation defects resulting in early, and in some cases, mid-stage embryonic arrest [12][13][14]17,18,[63][64][65][66][67]. In Ae.…”

“…The second is a symbiotic drive system termed cytoplasmic incompatibility (CI) that results in embryonic lethality when Wolbachia-infected males mate with uninfected females [10]. The lethality results from catastrophic, paternal defects in early embryogenesis including failure in condensation and segregation of paternal chromosomes, chromatin bridging, shredding of the paternal nuclei, early embryonic arrest, regional mitotic failures, and nuclear fallout [11][12][13][14][15][16][17][18]. Females carrying the same strain of Wolbachia rescue this lethality, thereby conferring a strong fitness advantage that spreads Wolbachia in natural host populations [19][20][21][22].…”