Biology subjects

Corti, P.

Publications and source records attributed to Corti, P..

4 recordsLinked to original sources

bioRxiv2026

Cytoglobin regulates ventricular morphogenesis and diastolic function through NO-sGC-cGMP signaling during development.

AimsHypoplastic left heart syndrome (HLHS) is a severe congenital heart disease characterized by ventricular hypoplasia and impaired cardiac function. Clinically, inhaled nitric oxide (NO) therapy is used to reduce pulmonary vascular resistance and improve cardiopulmonary stability in HLHS patients. However, whether NO signaling contributes to HLHS pathogenesis remains unknown. Cytoglobin (Cygb) is a heme-protein traditionally thought to limit NO bioavailability and downstream activation of the soluble guanylate cyclase (sGC) cyclic guanosine monophosphate (cGMP) signaling pathway. Unexpectedly, our recent work shows that Cygb enhances NO signaling through activation of NO synthase, leading to downstream activation of sGC-cGMP signaling. In zebrafish embryos, Cygb-dependent NO signaling is required for normal cilia motility and the establishment of correct cardiac laterality. Here, our aim was to determine whether Cygb-dependent NO-sGC signaling linked to cilia function regulates cardiac morphogenesis and contributes to ventricular hypoplasia in HLHS. Methods and ResultsWe found that loss of Cygb (cygb2) in zebrafish disrupts NO-sGC signaling during cardiogenesis, altering cardiac progenitor organization and migration within the anterior lateral plate mesoderm. Disruption of these processes impairs heart tube morphogenesis, thereby producing a compact ventricle wall characterized by increased wall thickness (despite preserved cardiomyocyte number) reduced ventricle size and decreased stroke volume, recapitulating key features of HLHS. Genetic disruption of the sGC -subunit (gucy1a1) and pharmacological NO scavenging phenocopy the cygb2 mutant phenotype, resulting in reduced cGMP levels, compact ventricular architecture and decreased stroke volume. Consistently, restoration of NO-sGC signaling in cygb2 mutants rescues early cardiac progenitor patterning, ventricular morphology and stroke volume. ConclusionsThese findings identify Cygb-dependent NO-sGC signaling as a critical developmental pathway for ventricular development and performance, temporally linking cardiac progenitor dynamics to cilia-dependent signaling associated with left-right patterning. This study further suggests that pharmacological activation of sGC may provide a therapeutic strategy for hypoplastic ventricular disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/711730v4_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@13a1515org.highwire.dtl.DTLVardef@3e1a6eorg.highwire.dtl.DTLVardef@1394ec2org.highwire.dtl.DTLVardef@161c81c_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2025

Measurement of nitric oxide production in mouse tracheal epithelial cell cultures differentiated at the air liquid interface.

Airway ciliary dysfunction often leads to impaired mucociliary clearance, a defect frequently associated with dysregulation of canonical nitric oxide (NO) signaling. Indeed, many airway diseases exhibit aberrant levels of exhaled NO, a feature commonly used as a diagnostic indicator in patients. While this measurement is routinely performed clinically, there is currently no validated approach to assess NO release from airway ciliated cells in vitro, limiting mechanistic studies of NO regulation and function. An established method to study airway diseases in vitro is the use of cultured mouse tracheal epithelial cells (MTECs) differentiated at the air-liquid interface (ALI). Here, using this model, we develop a protocol to measure NO released from ciliated cells and accumulated in apical mucus, collected from the ALI-differentiated cultures. Using established instrumentation for NO analysis and a triiodide-based assay, we quantify nitrite, a stable NO metabolite and biomarker of NO production. For assay validation, cells were treated with the NO donor Diethylenetriamine NONOate (DETA-NONOate or DETA/NO) or the NO synthase inhibitor N({omega})-Nitro-L-arginine methyl ester (L-NAME). Together, these approaches demonstrate that this method reliably detects NO in samples from ALI-differentiated airway epithelia, providing an accurate in vitro platform to quantify NO release and model diseases associated with abnormal NO metabolism. SUMMARYThe goal of this current protocol is to describe a cell culture-based method to study airway diseases associated with altered nitric oxide (NO) signaling. This method describes the quantification of NO in airway epithelia differentiated at the air-liquid interface (ALI) using a triiodide-based chemiluminescence assay.

molecular biology↗

bioRxiv2022

Misuse of Historical Data to Determine Past Distribution Range and Migratory Patterns of the Patagonian Huemul Misleads Conservation Targets

Historical information is widely used to understand mammals distribution dynamics and drivers, and it has been worldwide acknowledged by conservation programmes. Although these records have some limitations such as spatial and temporal accuracy, non-standardized sampling, geographical imprecisions, and levels of bias, they can fulfil a useful function to set reference conditions, priorities, and conservation goals. In the case of huemul (Hippocamelus bisulcus), an endemic cervid of shrubby and forested habitats from the Andes Mountains of southern Argentina and Chile, some reports suggest its historical presence in the steppe biome. This led Flueck et al. (2022) to assume that the past distribution of the huemul extended as far as the Atlantic coast and even in Tierra del Fuego, proposing that the altitudinal migratory tradition has been broken. Here, we carried out a qualitative and quantitative analysis of the written sources used by the authors to support their assumptions. We conclude that there are errors, uncertainties, and questionable interpretations on the use of historical data that do not add more value, instead, add mostly confusion with the misleading potential of conservation efforts on huemul.

zoology↗

bioRxiv2022

Myoglobin promotes cardiomyocyte differentiation through oxidatively modulating the Hippo Kinase Pathway

BackgroundWhile cardiomyocytes undergo terminal differentiation postnatally and rarely re-enter the cell cycle, the endogenous mechanisms that propagate differentiation and prevent de-differentiation remain unclear. The monomeric heme protein myoglobin, which stores oxygen and regulates reactive oxygen/nitrogen species balance in the heart, increases in expression by over 50% during cardiomyocyte differentiation. Though myoglobin deletion without significant compensation is embryonic lethal in mice, a role for the protein in regulating cardiomyocyte differentiation has not been tested. We hypothesized that myoglobin expression is required for cardiomyocyte differentiation and the loss of myoglobin enables de-differentiation. MethodsMyoglobin was genetically silenced in HL-1, H9C2 cells, and neonatal rat ventricular cardiomyocytes (NRVM) to examine myoglobin-dependent effects on differentiation, proliferation, and Hippo pathway signaling. A zebrafish model of Mb depletion was made using CRISPR-Cas9 to test the effect of myoglobin depletion on cardiac regeneration after apical resection injury in vivo. ResultsMyoglobin deletion in cultured cell lines and NRVM decreased the gene expression of cardiomyocyte differentiation markers (troponin, myosin light chain, and myosin heavy chain), upregulated markers of dedifferentiation (runx1 and dab2) and stimulated cell proliferation. Mechanistically, we show that the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, which activates the enzyme to phosphorylate the downstream Yes-associated protein (YAP) transcription factor, which prevents its transcriptional activity. Thus, the loss of myoglobin results in the de-phosphorylation and nuclear translocation of YAP, which propagates proliferation and fetal gene expression. In vivo, myoglobin-deficient zebrafish hearts recapitulated the increase in YAP signaling and showed accelerated regeneration at 20 days post apical injury. ConclusionWe a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation, and a regulator of the Hippo pathway. These findings suggest myoglobin as a potential target for strategies to enhance cardiac development and improve cardiac repair and regeneration.

cell biology↗