Modeling of large-scale hoxbb cluster deletions in zebrafish uncovers a role for segmentation pathways in atrioventricular boundary specification.

Hox genes orchestrate the segmental specification of the muscular circulatory system in invertebrates but it has not proven straightforward to decipher segmental parallels in the vertebrate heart. Recently, patients with HOXB gene cluster deletion were found to exhibit abnormalities including atrioventricular canal defects. Using CRISPR, we established a mutant with the orthologous hoxbb cluster deletion in zebrafish. The mutant exhibited heart failure and atrioventricular regurgitation at 5 days. Analyzing the four genes in the hoxbb cluster, isolated deletion of hoxb1b-/- recapitulated the cardiac abnormalities, supporting hoxb1b as the causal gene. Both in situ and in vitro data indicated that hoxb1b regulates gata5 to inhibit hand2 expression and ultimately is required to pattern the vertebrate atrioventricular boundary. Together, these data reveal a role for segmental specification in vertebrate cardiac development and highlight the utility of CRISPR techniques for efficiently exploring the function of large structural genomic lesions.

Antioxidant responses of triangle sail mussel Hyriopsis cumingii exposed to harmful algae Microcystis aeruginosa and hypoxia.

Bloom forming algae and hypoxia are considered to be two main co-occurred stressors associated with eutrophication. The aim of this study was to evaluate the interactive effects of harmful algae Microcystis aeruginosa and hypoxia on an ecologically important mussel species inhabiting lakes and reservoirs, the triangle sail mussel Hyriopsis cumingii, which is generally considered as a bio-management tool for eutrophication. A set of antioxidant enzymes involved in immune defence mechanisms and detoxification processes, i.e. glutathione-S-transferases (GST), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), lysozyme (LZM) in mussel haemolymph were analyzed during 14days exposure along with 7days depuration duration period. GST, GSH, SOD, GPX and LZM were elevated by toxic M. aeruginosa exposure, while CAT activities were inhibited by such exposure. Hypoxia influenced the immune mechanisms through the activation of GSH and GPX, and the inhibition of SOD, CAT, and LZM activities. Meanwhile, some interactive effects of M. aeruginosa, hypoxia and time were observed. Independently of the presence or absence of hypoxia, toxic algal exposure generally increased the five tested enzyme activities of haemolymph, except CAT. Although half of microcystin could be eliminated after 7days depuration, toxic M. aeruginosa or hypoxia exposure history showed some latent effects on most parameters. These results revealed that toxic algae play an important role on haemolymph parameters alterations and its toxic effects could be affected by hypoxia. Although the microcystin depuration rate of H. cumingii is quick, toxic M. aeruginosa and/or hypoxia exposure history influenced its immunological mechanism recovery.