The ion channel Trpc6a regulates the cardiomyocyte regenerative response to mechanical stretch.

Myocardial damage caused, for example, by cardiac ischemia leads to ventricular volume overload resulting in increased stretch of the remaining myocardium. In adult mammals, these changes trigger an adaptive cardiomyocyte hypertrophic response which, if the damage is extensive, will ultimately lead to pathological hypertrophy and heart failure. Conversely, in response to extensive myocardial damage, cardiomyocytes in the adult zebrafish heart and neonatal mice proliferate and completely regenerate the damaged myocardium.

PIEZO1 expression at the glio-vascular unit adjusts to neuroinflammation in seizure conditions.

Mechanosensors are emerging players responding to hemodynamic and physical inputs. Their significance in the central nervous system remains relatively uncharted. Using human-derived brain specimens or cells and a pre-clinical model of mesio-temporal lobe epilepsy (MTLE), we examined how the mRNA levels of the mechanosensitive channel PIEZO1 adjust to disease-associated pro-inflammatory trajectories.

Prolonged Piezo1 Activation Induces Cardiac Arrhythmia.

The rhythmical nature of the cardiovascular system constantly generates dynamic mechanical forces. At the centre of this system is the heart, which must detect these changes and adjust its performance accordingly. Mechanoelectric feedback provides a rapid mechanism for detecting even subtle changes in the mechanical environment and transducing these signals into electrical responses, which can adjust a variety of cardiac parameters such as heart rate and contractility.

Variations in the poly-histidine repeat motif of HOXA1 contribute to bicuspid aortic valve in mouse and zebrafish.

Bicuspid aortic valve (BAV), the most common cardiovascular malformation occurs in 0.5-1.2% of the population.

Expanding the phenome and variome of the ROBO-SLIT pathway in congenital heart defects: toward improving the genetic testing yield of CHD.

Background: Recent studies have shown the implication of the ROBO-SLIT pathway in heart development. Within this study, we aimed to further assess the implication of the ROBO and SLIT genes mainly in bicuspid aortic valve (BAV) and other human congenital heart defects (CHD).

Methods: We have analyzed a cohort of singleton exome sequencing data comprising 40 adult BAV patients, 20 pediatric BAV patients generated by the Pediatric Cardiac Genomics Consortium, 10 pediatric cases with tetralogy of Fallot (ToF), and one case with coarctation of the aorta.

The regenerative response of cardiac interstitial cells.

Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarction. Currently, it is becoming increasingly evident that cardiac interstitial cells play crucial roles during cardiac regeneration. To understand how interstitial cells behave during this process, we performed single-cell RNA sequencing of regenerating zebrafish hearts.

Deciphering DSC2 arrhythmogenic cardiomyopathy electrical instability: From ion channels to ECG and tailored drug therapy.

Background: Severe ventricular rhythm disturbances are the hallmark of arrhythmogenic cardiomyopathy (ACM), and are often explained by structural conduction abnormalities. However, comprehensive investigations of ACM cell electrical instability are lacking. This study aimed to elucidate early electrical myogenic signature of ACM.

Varying modalities of perinatal exposure to a pesticide cocktail elicit neurological adaptations in mice and zebrafish.

Epidemiological indications connect maternal and developmental presence or exposure to pesticides with an increased risk for a spectrum of neurological trajectories. To provide pre-clinical data in support of this hypothesis, we used two distinct experimental models. First, female and male mice were fed immediately prior to mating, and the resulting pregnant dams were continously fed during gestation and lactation periods using chow pellets containing a cocktail of six pesticides at tolerable daily intake levels.

Differential impact of dose-range glyphosate on locomotor behavior, neuronal activity, glio-cerebrovascular structures, and transcript regulations in zebrafish larvae.

The presence of glyphosate represents a debated ecotoxicological and health risk factor. Here, zebrafish larvae were exposed, from 1.5 to 120 h post-fertilization, to a broad concentration range (0.

Backbone Cyclization Turns a Venom Peptide into a Stable and Equipotent Ligand at Both Muscle and Neuronal Nicotinic Receptors.

Venom peptides are promising drug leads, but their therapeutic use is often limited by stability and bioavailability issues. In this study, we designed cyclic analogues of α-conotoxin CIA, a potent muscle nicotinic acetylcholine receptor (nAChR) blocker with a significantly lower affinity at the neuronal α3β2 subtype. Remarkably, all analogues retained the low nanomolar activity of native CIA toward muscle-type nAChRs but showed greatly improved resistance to degradation in human serum and, surprisingly, displayed up to 52-fold higher potency for the α3β2 neuronal nAChR subtype (IC 1.

New role of TRPM4 channel in the cardiac excitation-contraction coupling in response to physiological and pathological hypertrophy in mouse.

The transient receptor potential Melastatin 4 (TRPM4) channel is a calcium-activated non-selective cation channel expressed widely. In the heart, using a knock-out mouse model, the TRPM4 channel has been shown to be involved in multiple processes, including β-adrenergic regulation, cardiac conduction, action potential duration and hypertrophic adaptations. This channel was recently shown to be involved in stress-induced cardiac arrhythmias in a mouse model overexpressing TRPM4 in ventricular cardiomyocytes.

Piezo1 is required for outflow tract and aortic valve development.

Aims: During embryogenesis, the onset of circulatory blood flow generates a variety of hemodynamic forces which reciprocally induce changes in cardiovascular development and performance. It has been known for some time that these forces can be detected by as yet unknown mechanosensory systems which in turn promote cardiogenic events such as outflow tract and aortic valve development. PIEZO1 is a mechanosensitive ion channel present in endothelial cells where it serves to detect hemodynamic forces making it an ideal candidate to play a role during cardiac development.

Identification and characterization of two zebrafish Twik related potassium channels, Kcnk2a and Kcnk2b.

KCNK2 is a 2 pore domain potassium channel involved in maintaining cellular membrane resting potentials. Although KCNK2 is regarded as a mechanosensitive ion channel, it can also be gated chemically. Previous research indicates that KCNK2 expression is particularly enriched in neuronal and cardiac tissues.

Hair cell identity establishes labeled lines of directional mechanosensation.

Directional mechanoreception by hair cells is transmitted to the brain via afferent neurons to enable postural control and rheotaxis. Neuronal tuning to individual directions of mechanical flow occurs when each peripheral axon selectively synapses with multiple hair cells of identical planar polarization. How such mechanosensory labeled lines are established and maintained remains unsolved.

Synthesis, Structure and Biological Activity of CIA and CIB, Two α-Conotoxins from the Predation-Evoked Venom of .

Cone snails produce a fast-acting and often paralyzing venom that is usually injected into their prey or predator through a hypodermic needle-like modified radula tooth. Many diverse compounds are found in their venom including small molecules, peptides and enzymes. However, peptidic toxins called conotoxins (10⁻40 residues and 2⁻4 disulfide bonds) largely dominate these cocktails.

Reduced aggrecan expression affects cardiac outflow tract development in zebrafish and is associated with bicuspid aortic valve disease in humans.

Hemodynamic forces have been known for a long time to regulate cardiogenic processes such as cardiac valve development. During embryonic development in vertebrates, the outflow tract (OFT) adjacent to the ventricle comes under increasing hemodynamic load as cardiogenesis proceeds. Consequently, extracellular matrix components are produced in this region as the cardiac cushions form which will eventually give rise to the aortic valves.

Illuminating Phenylazopyridines To Photoswitch Metabotropic Glutamate Receptors: From the Flask to the Animals.

Phenylazopyridines are photoisomerizable compounds with high potential to control biological functions with light. We have obtained a series of phenylazopyridines with light dependent activity as negative allosteric modulators (NAM) of metabotropic glutamate receptor subtype 5 (mGlu). Here we describe the factors needed to achieve an operational molecular photoisomerization and its effective translation into and receptor photoswitching, which includes zebrafish larva motility and the regulation of the antinociceptive effects in mice.

OptoGluNAM4.1, a Photoswitchable Allosteric Antagonist for Real-Time Control of mGlu4 Receptor Activity.

OptoGluNAM4.1, a negative allosteric modulator (NAM) of metabotropic glutamate receptor 4 (mGlu4) contains a reactive group that covalently binds to the receptor and a blue-light-activated, fast-relaxing azobenzene group that allows reversible receptor activity photocontrol in vitro and in vivo. OptoGluNAM4.

High-resolution live imaging reveals axon-glia interactions during peripheral nerve injury and repair in zebrafish.

Neural damage is a devastating outcome of physical trauma. The glia are one of the main effectors of neuronal repair in the nervous system, but the dynamic interactions between peripheral neurons and Schwann cells during injury and regeneration remain incompletely characterized. Here, we combine laser microsurgery, genetic analysis, high-resolution intravital imaging and lattice light-sheet microscopy to study the interaction between Schwann cells and sensory neurons in a zebrafish model of neurotrauma.

Converging axons collectively initiate and maintain synaptic selectivity in a constantly remodeling sensory organ.

Sensory receptors are the functional link between the environment and the brain. The repair of sensory organs enables animals to continuously detect environmental stimuli. However, receptor cell turnover can affect sensory acuity by changing neural connectivity patterns.

piezo2b regulates vertebrate light touch response.

The sense of touch allows an organism to detect and respond to physical environmental stimuli. Mechanosensitive proteins play a crucial role in this process by converting the mechanical cue into a biological response. Recently, the Piezo family of stretch-activated ion channels has been identified as genuine mechanosensitive proteins.

Dynamic neuroanatomy at subcellular resolution in the zebrafish.

Genetic means to visualize and manipulate neuronal circuits in the intact animal have revolutionized neurobiology. "Dynamic neuroanatomy" defines a range of approaches aimed at quantifying the architecture or subcellular organization of neurons over time during their development, regeneration, or degeneration. A general feature of these approaches is their reliance on the optical isolation of defined neurons in toto by genetically expressing markers in one or few cells.