Biology subjects

Kraus, N.

Publications and source records attributed to Kraus, N..

3 recordsLinked to original sources

bioRxiv2025

A Developmental Mechanism Linking Heart Evolution and Congenital Defects

The evolution of double circulation in vertebrates required precise remodeling of the embryonic outflow tract (OFT), but the mechanisms enabling this transition remain unclear. Here, we show that oxygen acts as a developmental switch regulating apoptosis during OFT septation. In chick embryos, transient hypoxia disrupts apoptosis and produces atavistic phenotypes resembling ancestral vertebrate hearts with a single circulation. Comparative evidence suggests that developmental mode and associated oxygen levels facilitated OFT septation and the evolution of double circulation. This oxygen dependence also explains why CHD risk is elevated in hypoxic conditions, such as high-altitude pregnancy and maternal cardiovascular disease. Our findings establish a mechanistic link between heart development, evolution, and congenital defects, highlighting oxygen as both a driver of innovation and a source of vulnerability. This work challenges traditional views of cardiogenesis and underscores the need for integrative approaches to heart development and disease. SummaryThe evolution of warm-bloodedness in birds and mammals required profound physiological innovations, including a four-chambered heart with separate pulmonary and systemic circulation. This restructuring allowed for more efficient oxygen transport, supporting the high metabolic demands of sustained activity. While the anatomical and functional advantages of this transition are well understood, the developmental mechanisms that enabled it remain unclear. Here, we propose that changes in embryonic oxygen availability directly shaped the evolution of heart structure. We show that oxygen levels regulate programmed cell death during the remodeling of the hearts outflow tract, a critical process in the formation of separate circulatory circuits. Experimentally reducing oxygen in developing chick embryos prevented this programmed cell death, disrupted heart remodeling, and produced ancestral-like cardiac structures resembling those of cold-blooded vertebrates. These findings provide a developmental mechanism linking oxygen availability to heart evolution, explaining how changes in embryonic environment could have facilitated the transition to double circulation. They also suggest that congenital heart defects arise when this oxygen-sensitive developmental process is disrupted, offering new insights into why some heart malformations resemble ancestral states. By identifying oxygen as a key environmental cue in heart development, our study underscores the importance of non-genetic factors in shaping evolutionary transitions.

evolutionary biology↗

bioRxiv2021

Intercellular crosstalk regulating ARRB2/RARRES1 is involved in transition from fibrosis to cancer

Progressive fibrogenesis in chronic liver injury is often associated with cancer development. Beta-arrestin-2 (ARRB2) is a regulator of the profibrotic Angiotensin II type 1 receptor (AGTR1). The role of ARRB2 in liver fibrosis and in the transition from fibrosis to cancer is not fully understood and was investigated in this study. This study demonstrates that upregulation of the retinoic acid receptor responder 1 (RARRES1) in HSC mediated by ARRB2 leads to fibrosis. This process is driven by exosomal ARRB2 transfer to HSC, major fibrosis contributors, from injured hepatocytes, which highly express ARRB2. By contrast, downregulation of RARRES1 in hepatocytes induces malignant transformation and hepatocellular carcinoma (HCC) development. Consequently, Arrb2-deficient mice show higher number and size of liver tumors than wild-type mice in a hepatocellular carcinoma model with fibrosis. The identified relationship between ARRB2 and RARRES1 was observed in at least two species, including human cells and tissues in fibrosis and HCC and has a predictive value for survival in cancer patients. This study describes the discovery of a novel molecular pathway mediating the transition from fibrosis to cancer offering potential diagnostics and therapeutics.

molecular biology↗

bioRxiv2021

Anuran Heart Metamorphosis: Anatomical Support for Pulmonary Blood Separation in the Early Aquatic Phase

1.BackgroundIn both larval and adult anurans, blood separation and respiratory physiology have remained an enigma. While various blood separation mechanisms have been proposed, the same structure is seen as playing a key role: the conus arteriosus. However, previous findings on its internal structure are contradictory, depending on the specifics of the 2D imaging methods used by different authors. To resolve this problem, we used high-resolution X-ray microtomography of whole Bufo bufo specimens to acquire the first detailed 3D descriptions of this complex structure through metamorphosis. ResultsIn early tadpoles two small valvular openings develop at the ventricular-conal junction, providing two paths separated by the septum coni and continuing into the aortic arches. Thus, structures to support segregated pulmonary circulation are fully developed well before the lungs appear. The external gills undergo partial resorption and retreat asymmetrically into a gill chamber formed by a hyoidal cover, leaving only a single opening on the left side, the opercular spout. ConclusionsThe timing of events in Bufo circulatory development does not track the changing modes of respiration used by the developing tadpole. In particular, a system capable of double circulation carries only oxygen-depleted blood for a significant portion of the tadpole stage.

developmental biology↗