Deficient Signaling via Alk2 (Acvr1) Leads to Bicuspid Aortic Valve Development

Bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly in humans. Despite recent advances, the molecular basis of BAV development is poorly understood. Previously it has been shown that mutations in the Notch1 gene lead to BAV and valve calcification both in human and mice, and mice deficient in Gata5 or its downstream target Nos3 have been shown to display BAVs. Here we show that tissue-specific deletion of the gene encoding Activin Receptor Type I (Alk2 or Acvr1) in the cushion mesenchyme results in formation of aortic valve defects including BAV. These defects are largely due to a failure of normal development of the embryonic aortic valve leaflet precursor cushions in the outflow tract resulting in either a fused right- and non-coronary leaflet, or the presence of only a very small, rudimentary non-coronary leaflet. The surviving adult mutant mice display aortic stenosis with high frequency and occasional aortic valve insufficiency. The thickened aortic valve leaflets in such animals do not show changes in Bmp signaling activity, while Map kinase pathways are activated. Although dysfunction correlated with some pro-osteogenic differences in gene expression, neither calcification nor inflammation were detected in aortic valves of Alk2 mutants with stenosis. We conclude that signaling via Alk2 is required for appropriate aortic valve development in utero, and that defects in this process lead to indirect secondary complications later in life

The anatomy of the gastrointestinal tract of the African lungfish, Protopterus annectens

10.1002/ar.21154Anatomical Record29371146-115

The spleen of the African lungfish Protopterus annectens: Freshwater and aestivation

10.1007/s00441-012-1462-0Cell and Tissue Research3501143-156CTSR

Lympho-granulocytic tissue associated with the wall of the spiral valve in the African lungfish Protopterus annectens

10.1007/s00441-013-1746-zCell and Tissue Research3552397-407CTSR

The conus valves of the adult gilthead seabream (Sparus auratus)

The conus (bulbo-ventricular) valves of teleosts perform a key function in the control of blood backflow during ventricular diastole. However, the structural characteristics of these valves are almost unknown. This paper presents a systematic anatomical, histological and structural study of the conus valves of the adult gilthead seabream (Sparus auratus). S. auratus shows two major left and right valves consisting of the leaflet and the supporting sinus. Each valvar leaflet can be divided into a stout proximal body and a flap-like distal region. The proximal body is structured into three layers: a luminal fibrosa, a dense cellular core and a parietal fibrosa. The luminal fibrosa is a collagenous structure extending the entire length of the leaflet, while the parietal fibrosa is restricted to the most proximal area. The dense cellular core consists of fibroblastic cells and a matrix rich in glycoconjugates, collagen and elastin. The histochemical and structural data suggest that the luminal fibrosa bears most of the force associated with valvar closure, while the cellular core acts as a cushion dampening vibrations and absorbing the elastic recoil. The sinus wall is a fibrous layer which shows proximal–distal differences in thickness. It also shows compositional differences that can be related to mechanical function. We describe the presence of a fibrous cylinder formed by the sinus wall, the fibrous interleaflet triangles and the fibrous layer that covers the inner surface of the conus myocardium. This fibrous cylinder constitutes the structural nexus between the ventricle, the conus and the bulbus arteriosus, provides support for the conus valves and separates the valvar complex from the surrounding tissues. The structure of the conus valves in S. auratus is different from that found in other vertebrates. Anatomical similarities between the conus valves and the mammalian arterial valves are emphasized. Each phyletic group appears to have developed specific structures in order to perform similar functions

The conus arteriosus of the adult gilthead seabream (Sparus auratus)

This paper reports on the presence of the conus arteriosus in the heart of the adult gilthead seabream, Sparus auratus (Perciformes, Teleostei). The junctional region between the single ventricle and the bulbus arteriosus has been studied by conventional light microscopy, and by scanning and transmission electron microscopy. In addition, fluorescent phalloidin and antibodies against the muscle myosin heavy chains, laminin and collagen type IV have been used. The conus arteriosus is a distinct muscular segment interposed between the ventricle and the bulbus arteriosus. It is clearly different from the bulbus arteriosus due to its myocardial nature. It can also be distinguished from the ventricular myocardium because: (1) it has a conus shape; (2) it is formed by compact, well-vascularized myocardium; (3) it is surrounded on its inner and outer faces by fibrous layers rich in collagen and elastin; (4) it constitutes the anatomical support of the so-termed conus valves; (5) it shows intense staining for laminin and type-IV collagen; and (6) the myocardial cells located close to the inner fibrous layer are helicoidally arranged. By contrast, the ventricular myocardium is highly trabecular, lacks a compacta, shows no vessels, and presents barely detectable amounts of laminin and collagen type IV. The presence of a distinct conus arteriosus in the heart of an evolutionary advanced teleost species indicates that the conus is not a vestigial segment from the evolutionary or embryological points of view. The characteristic spatial arrangement of the conus myocytes strongly suggests that the conus is implicated in the mechanical performance of the conus valves