Search bioRxiv⌕ Search

Biology subjects

Jazwinska, A.

Publications and source records attributed to Jazwinska, A..

5 recordsLinked to original sources

The livebearers platyfish and swordtails partially regenerate their hearts with persistent scarring

Heart regeneration varies among vertebrates, with zebrafish serving as a reference species for efficient cardiac restoration. How this capacity diversified across teleosts is an emerging question, particularly following the recent identification of non-regenerative cardiac repair in medaka and cavefish. Here, we investigate heart restorative capacity following cryoinjury in two livebearers, platyfish and swordtails (Xiphophorus species), belonging to the Poeciliidae family. We demonstrate that their hearts lack the vascularized compact myocardium, a ventricular layer implicated in the restorative response in zebrafish. Following cryoinjury, both poeciliids failed to rapidly deposit fibrotic tissue that normally reinforces the damaged ventricle. This deficiency correlates with pronounced wound protrusion. Although the remaining myocardium displayed an initial proliferative response, subsequently deposited collagenous scar tissue permanently sealed the ventricular wall, precluding complete regeneration. Transcriptomic analysis identified several divergently regulated pathways between cryoinjured hearts of zebrafish and platyfish, most notably in immune response regulation. These differences were validated by delayed leukocyte infiltration and sustained inflammation in platyfish, contrasting with the rapid and self-resolving inflammatory response in zebrafish. Our findings demonstrate that Xiphophorus species have evolved hearts with compromised regenerative capacity, characterized by initial wound protrusion and permanent scarring. These results establish that lineage-specific evolutionary traits can profoundly shape regenerative competence across teleosts, with broad implications for understanding the mechanistic basis of cardiac repair. Highlights{middle dot} Viviparous poeciliids lack vascularized compact myocardium. {middle dot} Inflammation and fibrosis are delayed in the cryoinjured platyfish ventricle. {middle dot} Ventricular cryoinjury in Xiphophorus leads to transient bulging-type deformation. {middle dot} Failure to form a myocardial bridge results in permanent scarring.

developmental biology↗

Persistent ventricle partitioning in the adult zebrafish heart

The vertebrate heart integrates cells from the early-differentiating first heart field (FHF) and the later-differentiating second heart field (SHF) emerging from the lateral plate mesoderm. In mammals, this process forms the basis for the development of the left and right ventricle chambers and subsequent chamber septation. The single ventricle-forming zebrafish heart also integrates FHF and SHF lineages during embryogenesis, yet the contributions of these two myocardial lineages to the adult zebrafish heart remain incompletely understood. Here, we characterize the myocardial labeling of FHF descendants in both the developing and adult zebrafish ventricle. Expanding previous findings, late gastrulation-stage labeling using drl-driven CreERT2 recombinase with a myocardium-specific, myl7-controlled loxP reporter results in predominant labeling of FHF-derived outer curvature and the right side of the embryonic ventricle. Raised to adulthood, such lineage-labeled hearts retain broad areas of FHF cardiomyocytes in a region of the ventricle that is positioned at the opposite side to the atrium and encompasses the apex. Our data add to the increasing evidence for a persisting cell-based compartmentalization of the adult zebrafish ventricle even in the absence of any physical boundary.

developmental biology↗

Hydrodynamic stress and phenotypic plasticity of the zebrafish regenerating fin

Understanding how extrinsic factors modulate genetically encoded information to produce a specific phenotype is of prime scientific interest. In particular, the feedback mechanism between abiotic forces and locomotory organs during morphogenesis to achieve efficient movement is a highly relevant example of such modulation. The study of this developmental process can provide unique insights on the transduction of cues at the interface between physics and biology. Here, we take advantage of the natural ability of adult zebrafish to regenerate their amputated fins to assess its morphogenic plasticity upon external modulations. Using a variety of surgical and chemical treatments, we are able to induce phenotypic responses to the structure of the fin. In particular, fin cleft depth and the bifurcation of the bony rays are modulated by the surface area of the stump. To dissect the role of mechanotransduction in this process, we investigate the patterns of hydrodynamic forces acting on the surface of a zebrafish fin during regeneration by using particle tracking velocimetry on a range of biomimetic hydrofoils. This experimental approach enables us to quantitatively compare hydrodynamic stress distributions over flapping fins of varying sizes and shapes. As a result, viscous shear stress acting on the tip of the fin and the resulting internal tension are proposed as suitable signals for guiding the regulation of ray growth dynamics and branching pattern. Our findings suggest that mechanical forces are involved in the fine-tuning of the locomotory organ during fin morphogenesis.

biophysics↗

Oncogene-induced cardiac neoplasia shares similar mechanisms with heart regeneration in zebrafish

The human heart is a poorly regenerative organ and cardiac tumors are extremely rare. The zebrafish heart can restore its damaged myocardium through cardiomyocyte proliferation. Whether this endogenous capacity causes a susceptibility to neoplasia remains unknown. Here, we established a strategy to conditionally express the HRASG12V oncogene in zebrafish cardiomyocytes. The induction of this transgene in larvae or adult animals resulted in heart overgrowth with abnormal histology. The malformed ventricle displayed similar characteristics to the regenerative myocardium, such as enhanced cell-cycle entry, incomplete differentiation, reactivation of cardiac embryonic programs, expression of regeneration genes, oxidative metabolism changes, intramyocardial matrix remodeling and leucocyte recruitment. We found that oncogene-mediated cardiac tumorigenesis and cryoinjury-induced regeneration involve TOR signaling, as visualized by phosphorylation of its target ribosomal protein S6. The inhibition of TOR by rapamycin impaired regeneration and rescued from neoplasia. These findings demonstrate the existence of common mechanisms underlying the proliferative plasticity of zebrafish cardiomyocytes during advantageous organ restoration and detrimental tumorigenesis.

cell biology↗

Distribution and restoration of serotonin-immunoreactive paraneuronal cells during caudal fin regeneration in zebrafish

Aquatic vertebrates possess diverse types of sensory cells in their skin to detect stimuli in the water. In the adult zebrafish, a common model organism, the presence of such cells in fins has only rarely been studied. Here, we identified scattered serotonin (5-HT)-positive cells in the epidermis of the caudal fin. These cells were distinct from keratinocytes as revealed by their low immunoreactivity for cytokeratin and desmosome markers. Instead, they were detected by Calretinin (Calbindin-2) and Synaptic vesicle glycoprotein 2 (SV2) antibodies, indicating a calcium-regulated neurosecretory activity. Consistently, electron microscopy revealed abundant secretory organelles in desmosome-negative cells in the fin epidermis. Based on the markers, 5-HT, Calretinin and SV2, we referred to these cells as HCS-cells. We found that HCS-cells were spread throughout the entire caudal fin at an average density of 140 cells per mm2 on each fin surface. These cells were strongly enriched at ray bifurcations in wild type fins, as well as in elongated fins of another longfin mutant fish. To determine whether hydrodynamics play a role in the distribution of HCS-cells, we used an interdisciplinary approach and performed kinematic analysis. Measurements of particle velocity with a fin model revealed differences in fluid velocities between bifurcated rods and adjacent non-bifurcated regions. Therefore the accumulation of HCS-cells near bone bifurcations may be a biological adaptation for sensing of water parameters. The significance of this HCS-cell pattern is reinforced by the fact, that it is reestablished in the regenerated fin after amputation. Regeneration of HCS-cells was not impaired by the chemical inhibition of serotonin synthesis, suggesting that this neurotransmitter is not essential for the restorative process. In conclusion, our study identified a specific population of solitary paraneurons in the zebrafish fin, whose distribution correlates with fluid dynamics.

developmental biology↗