The role of macrophages during regeneration in zebrafish has been well-documented. Nevertheless, new evidence indicates that zebrafish macrophages are a heterogeneous population of cells, and that they can play different roles during immune responses and in tissue restoration after damage and infection. In this work, we first aimed to classify zebrafish macrophages according to their distribution in the larva during homeostasis and after tissue damage, distinguishing peripheral, and hematopoietic tissue resident macrophages. We discovered differences between the migratory behavior of these two macrophage populations both before and after tissue damage, triggered by the amputation of the tail fin. Further, we found a specific role for peripheral tissue-resident macrophages, and we propose that these cells contribute to tail fin regeneration by down-regulating inflammatory mediators such as interleukin-1b (il1b) and by diminishing reactive oxygen species (ROS) in the damage site. Our work suggests that specific macrophage populations recruited after tissue damage in zebrafish larvae can display different functions during both inflammation and tissue regeneration.

Highlights d Inflammatory cues and the microbiota modulate Gpr35 expression across species d LPA modulates GPR35-dependent functions in zebrafish and mouse macrophages d GPR35-expressing macrophages have a protective role during intestinal inflammation d GPR35 controls intestinal inflammation by inducing TNF and corticosterone

In vertebrates, damage to mechanosensory hair cells elicits an inflammatory response, including rapid recruitment of macrophages and neutrophils. While hair cells in amniotes usually become permanently lost, they readily regenerate in lower vertebrates such as fish. Damage to hair cells of the fish lateral line is followed by inflammation and rapid regeneration; however the role of immune cells in this process remains unknown. Here, we show that recruited macrophages are required for normal regeneration of lateral line hair cells after copper damage. We found that genetic ablation or local ablation using clodronate liposomes of macrophages recruited to the site of injury, significantly delays hair cell regeneration. Neutrophils, on the other hand, are not needed for this process. We anticipate our results to be a starting point for a more detailed description of extrinsic signals important for regeneration of mechanosensory cells in vertebrates. J. Cell. Biochem. 117: 1880-1889, 2016. © 2016 Wiley Periodicals, Inc.

The intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics to define how the transcriptomic landscape is spatially organized in the steady state and healing murine colon. At steady state conditions, we demonstrate a previously unappreciated molecular regionalization of the colon, which dramatically changes during mucosal healing. Here, we identified spatially-organized transcriptional programs defining compartmentalized mucosal healing, and regions with dominant wired pathways. Furthermore, we showed that decreased p53 activation defined areas with increased presence of proliferating epithelial stem cells. Finally, we mapped transcriptomics modules associated with human diseases demonstrating the translational potential of our dataset. Overall, we provide a publicly available resource defining principles of transcriptomic regionalization of the colon during mucosal healing and a framework to develop and progress further hypotheses.