1,721,118 research outputs found
Transcription factor FoxC2 demarcates the jugular lymphangiogenic region in avian embryos
No full textIn the human, mutations of the forkhead winged-helix transcription factor FOXC2 cause the lymphedema-distichiasis syndrome, which is characterized by a double row of eyelashes and pubertal onset lymphedema of the legs due to hyperplasia and malformation of lymphatic collectors. While a function of FOXC2 for the differentiation of lymphatic collectors is well documented, recent studies have indicated an early function for the sprouting of lymphatics from embryonic veins. We studied the expression of FoxC2 in early avian embryos and compared its expression pattern with that of the homeobox transcription factor Prox1, which is essential for lymphatic endothelial cell (LEC) development. We show that FoxC2 demarcates a segment of the somatopleura in the cervical region on embryonic day (ED) 3, before Prox1 is expressed. On ED 4, its expression domain coincides with that of Prox1 in the jugular region. This region is characterized by the confluence of Tie2-positive anterior and posterior cardinal veins. It has been shown that Prox1 expression in a subpopulation of venous endothelial cells induces transdifferentiation into LECs. Our data suggest that FoxC2, in addition to its late functions during lymph collector differentiation, has an early function during lymphendothelial commitment of venous ECs in the jugular region.NICHD NIH HHS [N01-HD-6-2915
25 years of criticality in neuroscience — established results, open controversies, novel concepts
No full textBetween Perfectly Critical and Fully Irregular: A Reverberating Model Captures and Predicts Cortical Spike Propagation
No full textDevelopment and engineering of lymphatic endothelial cells: Clinical implications
No full textStudies on the lymphatic endothelium have been hampered by the difficulty to identify lymphatic endothelial cells (LECs) and to distinguish them from blood vascular endothelial cells (BECs). The situation was greatly improved by the identification of molecules with high specificity for LECs. A great deal of progress in the field of lymphangiogenesis research has been due to the detection of lymphangiogenic growth factors and their receptors, and there is growing evidence that these molecules are also involved in tumor-induced lymphangiogenesis and lymphatic dissemination of tumor cells. There is a considerable spectrum of congenital and acquired lymphedema-lymphangiodysplasia syndromes ranging from primary aplasia, hypoplasia and hyperplasia to secondary (acquired) obstructive, obliterative and surgical hindrance of lymph drainage. Consequently, there are a number of clinical applications for therapeutics that either inhibit or induce lymphangiogenesis. Although natural lymphatic regeneration is mostly very efficient, engineering of LECs may be useful in cases of lymphatic aplasia or hypoplasia. To achieve these goals, studies on the embryonic development and differentiation of LECs will reveal the key regulatory factors that need to be targeted
The lymphatic vascular system: Secondary or primary?
No full textIt has generally been accepted that the blood vascular system is primary and the lymphatic vascular system secondary. Diseases of the blood vascular system are the leading cause for mortality and morbidity in developed nations. In contrast, lymphedema is seldom life-threatening and can generally be well-managed by combined physiotherapy. During ontogeny, the blood vessels and the heart develop much earlier than the lymphatic vessels. However, there is growing evidence that the first vascular system occurring during ontogeny and phylogeny has lymphatic functions. Defense mechanisms are crucial for all organisms irrespective of their size. Macrophages precede the emergence of erythrocytes during ontogeny, and their circulation in the hemolymphatic (more accurately, lymphohematic) system of insects, which do not possess erythrocytes, shows that the lymphatic function is primary whereas the nutritive function is secondary, needed only in larger organisms. In molluscs and arthropods, which have an open vascular system, hemocyanin has both oxygen transporting and defense functions. In vertebrates, the early blood vessels have structural characteristics of lymphatics and express the lymphendothelial receptor flt-4 (Vascular Endothelial Growth Factor Receptor-3). Later, flt-4 becomes restricted to the definitive lymphatics, which are either formed from the primary vessels or from mesodermal lymphangioblasts. The primary lymphatic function has become overruled by the nutritive function in blood vessels of larger animals. The circular movement of cells is driven by a blood heart, which, however, is not an unique organ. Lymph hearts are present in lower vertebrates, still develop transiently in birds, and are vestigial in the contractile lymphangion which "circulates" immune cells. We conclude that the definitive lymphatics are perhaps secondary in mammals, but the blood vascular system seems to develop on the basis of an ancestral lymphatic system with lymph hearts
Left-Right Asymmetry in Embryonic Development and Breast Cancer: Common Molecular Determinants?
No full textDevelopment and growth of the foot lumbricalis muscle: a histological study using human foetuses
No full textBackground: Our group has shown early development of the hand lumbricalis and hypothesized that, at midterm, the lumbricalis (LU) bundles flexor tendons to provide a configuration of "one tendon per one finger" (Cho K.H. Folia Morphol. 2012; 71, 3: 154-163). However, the study concentrated on the hand and contained no sections of near-term foetuses.
Materials and methods: The present examination of paraffin-embedded tangential sections along the planta from 25 embryos and foetuses at 6-40 weeks (15-320 mm crown-rump length) demonstrated that, at 8 weeks, the initial foot LU appeared in the proximal side of the common tendinous plate of all five deep tendons.
Results: After midterm, a drastic three-phase change occurred at the muscle origin: 1) the LU originated from each of the flexor digitorum longus tendon (FDLT), but abundant tenocyte candidates separated the muscle fibre from the tendon collagen bundle; 2) the LU arose from the covering fascia depending on increased thickness of the muscle; and 3) the LU muscle fibres intermingled with tendon collagen bundles and partly surrounded the tendon. Simultaneously, a dividing site of the FDLT migrated distally to accelerate the changes at the LU origin. These phases did not always correspond to the size of foetus after 30 weeks.
Conclusions: Consequently, in contrast to the hand LU, the delayed changes in the foot were characterised by involvement of the LU origin into a single common part of the FDLT. The quadratus plantae muscle fibres did not attach to the LU at any phase, and connected with the fourth and fifth toe tendons.Depto. de Anatomía y EmbriologíaFac. de MedicinaTRUEpu
Lymphatics and Inflammation
No full textInflammation is a local or systemic tissue reaction caused by external or internal stimuli with the objective to remove the noxa, inhibit its further dissemination and eventually repair damaged tissue. Blood vessels and perivascular connective tissue are important regulators of the inflammatory process. After a short initial ischemic phase, inflamed tissue is characterized by hyperaemia and increased permeability of capillaries. Therefore, blood vessels have been in the focus of inflammation research for quite some time, whereas lymphatic vessels have been neglected. Their reactivity is not immediately obvious, and, their identification within the tissue has hardly been possible until lymphatic endothelial cell (LEC)-specific molecules have been identified a few years ago. This has opened up the possibility to study lymphatics in normal and diseased tissues, and to isolate LECs for transcriptome and proteome analyses. Initial studies now provide evidence that lymphatics are not just a passive route for circulating lymphocytes, but seem to be directly involved in both the induction and the resolution of inflammation. This review provides a summary on the basics of inflammation, the structure of lymphatics and their molecular markers, human inflammation-associated diseases and their relation to lymphatics, animal models to study the interaction of lymphatics and inflammation, and finally inflammation-associated molecules expressed in LECs. The integration of lymphatics into inflammation research opens up an exciting new field with great clinical potential
Three-dimensional tissue culture as an experimental model for the evaluation of angiogenic factors
No full textPurpose and Methods: Angiogenesis is the formation of new vessels from preexisting capillaries. Under physiological conditions angiogenesis is a rare event in the adult except in females during their reproductive period, where controlled angiogenesis occurs in the ovary during maturation of the follicle and formation of the corpus luteum and in the uterus during the endometrial secretory phase. During pregnancy angiogenesis occurs in the placenta and the growing mammary glands. Angiogenesis is essential for fertility and to ensure an adequate blood Supply for the growing embryo. In order to improve angiogenesis it is essential to know the underlying molecular mechanisms. We know by now that angiogenesis is controlled by the concerted interaction of a variety of factors (e.g. growth factors, extracellular matrix proteins, and matrix proteases). Here, we present and metabolically characterize an experimental system that allows investigation of individual factors as well as their concerted interaction on the process of terminal cell differentiation. Conclusion: By means of this three dimensional experimental system the function of the extracellular matrix, as it is understood today, is clearly mimicked. It serves as a cellular lattice on the one hand but also as a reservoir for growth factors that are sequestered and released according to the cellular metabolism
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