Misato Fujita

Filamin C plays an essential role in the maintenance of the structural integrity of cardiac and skeletal muscles, revealed by the medaka mutant zacro

Filamin C is an actin-crosslinking protein that is specifically expressed in cardiac and skeletal muscles. Although mutations in the filamin C gene cause human myopathy with cardiac involvement, the function of filamin C in vivo is not yet fully understood. Here we report a medaka mutant, zacro (zac), that displayed an enlarged heart, caused by rupture of the myocardiac wall, and progressive skeletal muscle degeneration in late embryonic stages. We identified zac to be a homozygous nonsense mutation in the filamin C (flnc) gene. The medaka filamin C protein was found to be localized at myotendinous junctions, sarcolemma, and Z-disks in skeletal muscle, and at intercalated disks in the heart. zac embryos showed prominent myofibrillar degeneration at myotendinous junctions, detachment of myofibrils from sarcolemma and intercalated disks, and focal Z-disk destruction. Importantly, the expression of γ-actin, which we observed to have a strong subcellular localization at myotendinous junctions, was specifically reduced in zac mutant myotomes. Inhibition of muscle contraction by anesthesia alleviated muscle degeneration in the zac mutant. These results suggest that filamin C plays an indispensable role in the maintenance of the structural integrity of cardiac and skeletal muscles for support against mechanical stress.

Vascular anatomy of the developing medaka, Oryzias latipes: a complementary fish model for cardiovascular research on vertebrates.

The zebrafish has become a very useful vertebrate model for cardiovascular research, but detailed morphogenetic studies have revealed that it differs from mammals in certain aspects of the primary circulatory system, in particular, the early vitelline circulation. We searched for another teleost species that might serve as a complementary model for the formation of these early primary vessels. Here (and online at http://www.shigen.nig.ac.jp/medaka/atlas/), we present a detailed characterization of the vascular anatomy of the developing medaka embryo from the stage 24 (1 day 20 hr) through stage 30 (3 days 10 hr). Three‐dimensional images using confocal microangiography show that the medaka, Oryzias latipes, follows the common embryonic circulatory pattern consisting of ventral aorta, aortic arches, dorsal aorta, transverse vessels, vitelline capillary plexus, and marginal veins. The medaka, thus, may serve as a valuable model system for genetic analysis of the primary vasculature of vertebrates. Developmental Dynamics 235:734–746, 2006.

Migration of mesenchymal cell fated to blastema is necessary for fish fin regeneration

Urodeles and fish have higher regeneration ability in a variety of tissues and organs than do other vertebrate species including mammals. Though many studies have aimed at identifying the cellular and molecular basis for regeneration, relatively little is known about the detailed cellular behaviors and involved molecular basis. In the present study, a small molecule inhibitor was used to analyzed the role of phosphoinositide 3‐kinase (PI3K) signaling during regeneration. We showed that the inhibitor disrupted the formation of blastema including the expression of characteristic genes. The failure of blastema formation was due to the impaired migration of mesenchymal cells to the distal prospective blastema region, although it had a little affect on cell cycle activation in mesenchymal cells. Moreover, we found that the epidermal remodeling including cell proliferation, distal cell migration and Akt phosphorylation was also affected by the inhibitor, implying a possible involvement of epidermis for proper formation of blastema. From these data, we propose a model in which distinct signals that direct the cell cycle activation, mesenchymal cell migration and epidermal remodeling coordinate together to accomplish the correct blastema formation and regeneration.