The careg element reveals a common regulation of regeneration in the zebrafish myocardium and fin

Abstract

The existence of common mechanisms regulating organ regeneration is an intriguing concept. Here we report on a regulatory element that is transiently activated during heart and fin regeneration in zebrafish. This element contains a ctgfa upstream sequence, called careg, which is induced by TGFβ/Activin-β signalling in the peri-injury zone of the myocardium and the fin mesenchyme. In addition, this reporter demarcates a primordial cardiac layer and intraray osteoblasts. Using genetic fate mapping, we show the regenerative competence of careg-expressing cells. The analysis of the heart reveals that the primordial cardiac layer is incompletely restored after cryoinjury, whereas trabecular and cortical cardiomyocytes contribute to myocardial regrowth. In regenerating fins, the activated mesenchyme of the stump gives rise to the blastema. Our findings provide evidence of a common regenerative programme in cardiomyocytes and mesenchyme that opens the possibility to further explore conserved mechanisms of the cellular plasticity in diverse vertebrate organs.

Zebrafish fin regeneration involves transient serotonin synthesis

“…Finally, we assessed deposition of serotonin after inhibition of another pathway, TGFβ/Activin‐βA, which is also essential for regeneration, but most likely acts in parallel to FGF signaling . The treatment of fins with 10 μM SB431542, a validated TGFβ/Activin‐βA inhibitor, for 2 days starting from 2 dpa impaired progression of regeneration without affecting serotonin in the blastema (Figure G and H).…”

“…Finally, we assessed deposition of serotonin after inhibition of another pathway, TGFβ/Activin-βA, which is also essential for regeneration, but most likely acts in parallel to FGF signaling. 5 The treatment of fins with 10 μM SB431542, a validated TGFβ/Activin-βA inhibitor, [30][31][32] for 2 days starting from 2 dpa impaired progression of regeneration without affecting serotonin in the blastema ( Figure 6G and H). Thus, inhibition of regeneration in an FGF-independent manner does not affect serotonin expression, and we, therefore, conclude that the absence of serotonin in the blastema after interference with FGF and retinoic acid signaling is pathway specific.…”

“…Importantly, both these structures originate from the mobilized stump tissues. The wound epidermis derives from migrating epithelial cells at the site of injury, while the blastema arises by the conversion of local non‐dividing cells into lineage‐restricted proliferating cells, which give rise to the outgrowth . The blastema comprises mesenchymal cells and osteoblasts, both of which are components of connective tissue in the fin.…”

“…The wound epidermis derives from migrating epithelial cells at the site of injury, while the blastema arises by the conversion of local non-dividing cells into lineage-restricted proliferating cells, which give rise to the outgrowth. [3][4][5] The blastema comprises mesenchymal cells and osteoblasts, both of which are components of connective tissue in the fin. The distal-most part of the regenerative outgrowth is thought to act as an organizer through its signaling activity, whereas the proximal blastema comprises the proliferation and re-differentiation zone.…”

Tissue Regeneration Enhancer Elements: A Way to Unlock Endogenous Healing Power

“…heart layer (a primordial cardiac layer) (Chiou et al, 2006;Mateus et al, 2015;Pfefferli and Jazwinska, 2017). However, various injuries ectopically up-regulated the reporter expression in the notochord, fin, and heart.…”