Symbiosis with Dinoflagellates Alters Cnidarian Cell-Cycle Gene Expression

In the cnidarian-dinoflagellate symbiosis, hosts show altered expression of genes involved in growth and proliferation when in the symbiotic state, but little is known about the molecular mechanisms that underlie the host’s altered growth rate. Using tissue-specific transcriptomics, we determined how symbiosis affects expression of cell cycle-associated genes, in the model symbiotic cnidarian Exaiptasia diaphana (Aiptasia). The presence of symbionts within the gastrodermis elicited cell-cycle arrest in the G1 phase in a larger proportion of host cells compared with the aposymbiotic gastrodermis. The symbiotic gastrodermis also showed a reduction in the amount of cells synthesizing their DNA and progressing through mitosis when compared with the aposymbiotic gastrodermis. Host apoptotic inhibitors (Mdm2) were elevated, while host apoptotic sensitizers (c-Myc) were depressed, in the symbiotic gastrodermis when compared with the aposymbiotic gastrodermis and epidermis of symbiotic anemones, respectively. This indicates that the presence of symbionts negatively regulates host apoptosis, possibly contributing to their persistence within the host. Transcripts (ATM/ATR) associated with DNA damage were also downregulated in symbiotic gastrodermal tissues. In epidermal cells, a single gene (Mob1) required for mitotic completion was upregulated in symbiotic compared with aposymbiotic anemones, suggesting that the presence of symbionts in the gastrodermis stimulates host cell division in the epidermis. To further corroborate this hypothesis, we performed microscopic analysis using an S-phase indicator (EdU), allowing us to evaluate cell cycling in host cells. Our results confirmed that there were significantly more proliferating host cells in both the gastrodermis and epidermis in the symbiotic state compared with the aposymbiotic state. Furthermore, when comparing between tissue layers in the presence of symbionts, the epidermis had significantly more proliferating host cells than the symbiont-containing gastrodermis. These results contribute to our understanding of the influence of symbionts on the mechanisms of cnidarian cell proliferation and mechanisms associated with symbiont maintenance.