Kvederaviciute, K. | bioRxiv Science

bioRxiv2025

Epicardial Tcf21 facilitates cardiomyocyte dedifferentiation and heart regeneration in zebrafish

Unlike mammals, zebrafish (Danio rerio) are able to regenerate their hearts after injury, making them an excellent model organism for studying the molecular mechanisms underlying heart regeneration. Epicardium, the outermost layer of the heart, is an essential player in this process. Injury-induced epicardium activation, characterized by the expression of embryonic epicardial marker genes including tcf21 supports cardiac regeneration by providing various cell types and releasing paracrine signals that promote the restoration of damaged tissue. However, the molecular mechanisms involved in this process are insufficiently understood. In this study, we describe a conditional tcf21flox allele and use it to investigate the role of Tcf21 in heart regeneration. By employing 4-hydroxytamoxifen inducible CreERT2 recombinase, we eliminated tcf21 expression in adult fish. Our findings indicate that loss of this transcription factor reduces the presence of dedifferentiated cardiomyocytes in the injury area and impairs heart regeneration. This work provides new insights into the molecular basis of the epicardial response to heart injury and its role in guiding heart regeneration.

developmental biology↗

bioRxiv2021

Dual control of MAPK activities by AP2C1 and MKP1 MAPK phosphatases regulates defence responses in Arabidopsis

Mitogen-activated protein kinase (MAPK) cascades transmit environmental signals and induce stress and defence responses in plants. These signalling cascades are negatively controlled by specific phosphatases of the type 2C Ser/Thr protein phosphatase (PP2C) and dual-specificity phosphatase (DSP) families that inactivate stress-induced MAPKs; however, the interplay between phosphatases of these different types has remained unknown. Our work reveals that different Arabidopsis MAPK phosphatases, the PP2C-type AP2C1 and the DSP-type MKP1, exhibit both specific and overlapping functions in plant stress responses. Each single mutant and ap2c1 mkp1 double mutant displayed enhanced wound-induced activation of MAPKs MPK3, MPK4, and MPK6, as well as induction of a set of transcription factors. Moreover, ap2c1 mkp1 double mutants show an autoimmune-like response, associated with elevated levels the stress hormones salicylic acid and ethylene, and of the phytoalexin camalexin. Interestingly, this phenotype is reduced in ap2c1 mkp1 mpk6 triple mutants, suggesting that the autoimmune-like response is due to MPK6 misregulation. We conclude that the evolutionarily distant MAPK phosphatases AP2C1 and MKP1 contribute crucially to the tight control of MPK6 activity, ensuring appropriately balanced stress signalling and suppression of autoimmune-like responses during plant growth and development. HighlightDouble MAPK phosphatase mutant plants ap2c1 mkp1 exhibit constitutive, autoimmune-like stress responses, dependent on their substrate MAPK MPK6.

plant biology↗