Tcf transcription factors interact with -catenin and Armadillo to mediate Wnt/Wingless signaling. We now report the characterization of genes encoding two murine members of the Tcf family, mTcf-3 and mTcf-4. mTcf-3 mRNA is ubiquitously present in embryonic day 6.5 (E6.5) mouse embryos but gradually disappears over the next 3 to 4 days. mTcf-4 expression occurs first at E10.5 and is restricted to di-and mesencephalon and the intestinal epithelium during embryogenesis. The mTcf-3 and mTcf-4 proteins bind a canonical Tcf DNA motif and can complex with the transcriptional coactivator -catenin. Overexpression of Wnt-1 in a mammary epithelial cell line leads to the formation of a nuclear complex between -catenin and Tcf proteins and to Tcf reporter gene transcription. These data demonstrate a direct link between Wnt stimulation and -catenin/Tcf transcriptional activation and imply a role for mTcf-3 and -4 in early Wnt-driven developmental decisions in the mouse embryo.
The histogenesis of the separation between atrial and ventricular myocardium at the atrioventricular junction in the developing human heart has been investigated immunohistochemically by using monoclonal antibodies specific for atrioventricular cushion tissue, mesenchymal cells, atrial and ventricular myocardium, and myocardium of the primary ring. It was found that the insulation between the muscle masses of atrium and ventricle is established by the fusion of the tissues of the atrioventricular sulcus (located at the epicardial side of the junctional myocardium) with those of the atrioventricular cushions (located at the endocardial side of the junctional myocardium). This process takes place at the ventricular margin of the myocardium of the atrioventricular canal. The separation of atrial and ventricular myocardium starts at approximately 7 weeks of development in the anteromedial portion of the right atrioventricular junction and is largely completed around the 12th week of development. The only remaining myocardial continuity between atrial and ventricular myocardium is the atrioventricular axis of conduction. Our findings show that the nonmuscular part of the developing leaflets of the atrioventricular valves derives from the atrioventricular cushions and that the tissues of the atrioventricular groove do not contribute to the development of these leaflets.
(1) The expression of neurofilaments can be used to delineate the nodal area in the intact SAN but is not sufficiently sensitive for characterizing all individual isolated nodal cells. (2) A fundamentally different organization of the SAN is presented: The gradual increase in density of atrial cells from the dominant area toward the crista terminalis in the SAN causes a gradual increase of atrial electrotonic influence that may be an important cause of the gradual transition of the nodal to the atrial type of action potential.
The purpose of the present study was to investigate the sites in the hypothalamus where the suprachiasmatic nucleus (SCN) may influence corticosteroid secretion. In spite of the well established, SCN-mediated, daily rhythms in adrenocorticotrophic hormone (ACTH) and corticosteroid secretion, previous studies determining the projections of the suprachiasmatic nucleus failed to illustrate direct connections with corticotrophin-releasing hormone neurons (CRH). In order to identify where in the central nervous system the SCN may influence corticosteroid secretion, areas were selected that contained SCN efferents contacting neurons involved in the stress response. To achieve this in the present study, SCN efferents were visualized by Pha-L tract-tracing, together with the neurons involved in the stress response by immunocytochemical staining for c-fos protein. The sites where these efferents contacted c-fos-positive neurons were established by light microscopic double staining and electron microscopic immunocytochemical studies. It appeared that apart from the medial parvocellular area of the paraventricular nucleus (PVN) of the hypothalamus, many more regions showed fos-positive neurons. Sites where SCN efferents contacted such neurons are limited only to areas immediately adjacent to these putative CRH neurons but are not concentrated on these neurons themselves. These areas consist of the periventricular and rostral PVN together with the dorsomedial hypothalamus: all three regions are known to project into the PVN. Therefore, it is concluded that the SCN transmits its information related to corticosteroid secretion via interneurons in and around the PVN to the CRH-containing neurons, rather than by a direct interaction with these neurons themselves.
The results indicate that alpha-SMA, calponin, and desmin are involved in the myofibrillar development in rat heart. The presence of spatiotemporal differences in the expression of these proteins reveals regional differences in the developmental timing of cardiomyocyte maturation. The maturation process extends from the compact myocardium in the IVS to the left and right ventricular free walls, whereas the atrioventricular junction, the ventricular trabeculae, and developing ventricular conduction system show a relatively slow maturation. Smooth-muscle proteins may contribute to the slow shortening speed that is characteristic of the embryonic myocardium.
Members of the Sox gene family of transcription factors are defined by the presence of an 80 amino acid homology domain, the High Mobility Group (HMG) box. Here we report the cloning and initial analysis of murine Sox-13 . The 984 amino acids Sox-13 protein contains a single HMG box, a leucine zipper motif and a glutamine-rich stretch. These characteristics are shared with another member of the Sox gene family, Sox-6. High level embryonic expression of Sox-13 occurs uniquely in the arterial walls of 13.5 days post coitum (dpc) mice and later. Low level expression was observed in the inner ear of 13.5 dpc mice and in a limited number of cells in the thymus of 16.5 dpc mice, from which Sox-13 was originally cloned. At 18.5 dpc, Sox-13 is expressed in the tracheal epithelium below the vocal cord and in the hair follicles. The Sox-13 protein binds to the consensus HMG box motif, AACAAAG, but does not transactivate transcription through a concatamer of this motif. Sox-13, like other members of the Sox family likely plays an important role in development.
SUMMARY A patient with Waldenstrom's macroglobulinaemia presented with visual reduction in both eyes. The funduscopic and angiographic demonstrations of venous engorgement ('string of sausages'), retinal haemorrhages at all levels, retinal and disc oedema, and serous detachment of the maculas were consistent with this diagnosis. The cryoprecipitation of the immunoglobulin at a temperature slightly below body temperature precluded routine blood studies and plasmapheresis. Plasmapheresis was ultimately performed without difficulty with the patient and equipment at 88°F (31°C). Despite marked improvement in the funduscopic and angiographic appearance of the retina, perifoveal capillary nonperfusion and serous elevation of the macula persisted. Even when the maculas flattened in both eyes, no visual recovery occurred. Early diagnosis, even on a clinical basis when laboratory studies cannot be performed, and early plasmapheresis to reduce serum viscosity are warranted to prevent intravascular occlusion in the perifoveal capillary bed, deposition of immunoglobulin in the retina, and transudation in the subretinal space.
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