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Notes: [Auszug] Early Drosophila embryogenesis is initiated by 13 rapid and synchronous nuclear cleavages which occur within a syncytium. At the end of the 13th cycle, cellular membranes begin to form at the periphery of the embryo; their completion defines the cellular blastoderm10. Soon after, gastrulation ...

Notes: [Auszug] Antibodies directed against chick FN have been previously used to demonstrate the presence of FN on the inner surface of the ectoderm of gastrulating Pleurodeles embryos7. Specific antibodies to Ambystoma mexicanum plasma FN were prepared (Fig. 1) to improve the immunofluorescence staining. In ...

Notes: Conclusion Without the establishment and maintenance of specialized junctions, the specific association of which characterizes epithelial cells, the epithelium-specific polarity would not exist. The major goal of this review has been to develop the idea that relationships between CAMs and junctions do occur. Although CAMs were first described as morphoregulatory molecules essential for the normal development of the embryo, it has become evident that they may also have a role in epithelial cohesiveness as specialized junctions do. The arguments that suggest relationships between Ca2+-dependent CAMs (cadherins) and junctions are the following: (i) Some junction-specific molecules and cadherins are identical. (ii) In some cases, the expression of specific cadherins at the cell surface leads to the establishment of specialized junctions. (iii) The inhibition of cadherin-mediated adhesion blocks the establishment of specialized junctions. (iv) Junctions and cadherins are equally sensitive to Ca2+ ions. Moreover, chelation of external Ca2+ ions dissociates epithelial cells. Despite the existing evidence suggesting that the expression of cadherins could regulate the assembly of junctions, the hierarchy of events leading to epithelial cohesiveness is largely unknown. Furthermore, it is not yet clear whether the mechanisms of epithelial adhesion are regulated at the transcriptional, translational or posttranslational level. Moreover, further studies will have to shed new light on the biological factors involved in the creation and maintenance of epithelial cohesiveness. But the intensive effort of several laboratories will probably be fruitful in the near future and will give further insights into the mechanisms that regulate the assembly/disassembly of junctions and the modulation of cadherins in physiological as well as pathological situations.

Notes: [Auszug] Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic ...

Notes: [Auszug] Fibroblast growth factor receptor 3 (FGFR3) belongs to a family of structurally related tyrosine kinase receptors encoded by four different genes. These receptors are glycoproteins composed of two to three extracellular immunoglobulin (Ig)-like domains, a transmembrane domain and a split ...

Notes: [Auszug] During gastrulation in Drosophila and mammals, cells migrate from an epithelial-like structue to spatially reorganize one of the three main embryonic layers, the mesoderm. The migratory nature of these cells, which give rise to blood and muscle, has prompted comparisons to metastatic cells. And it ...

Notes: [Auszug] In the chick, cell and plexiform layers of the central portion of the retina are formed between the sixth and ninth days of embryonic life9,10. Although many cells have left the mitotic cycle by day 6 (ref. 9), all remain in a single nuclear or 'matrix' layer. Retinae dissected from White Leghorn ...

Notes: Abstract Various mechanisms of epithelial cell plasticity in morphogenesis have been studied at the genetic and molecular levels. Several control genes have been identified including genes encoding transcription factors and growth factor receptors. These mechanisms may be reactivated during the progression of carcinomas. One of the mechanisms underlying epithelial plasticity is the epithelial–mesenchymal transition. This process has been extensively studied using the NBT-II bladder carcinoma cell line. Cells of this line undergo a reversible transition following exposure to several growth factors including FGF1, EGF, TGFα and SF/HGF, which activate tyrosine kinase surface receptors. Two separate transduction pathways have been identified. The transient activation of c-Src is involved in cytoskeleton remodeling whereas the Ras pathway controls the transcription of genes such as the transcription factor Slug which is involved in the internalization of desmosomes. These two pathways cooperate to induce the morphological transition, scattering and locomotion of fibroblast-like cells. Growth/scatter factor-producing NBT-II cells are more invasive than cells that do not contain this factor, in orthotopic confrontation assay. In vivo, these cells are very tumorigenic and may confer a more malignant phenotype on parental cells via a community effect. The role of several growth factors and their receptors has been investigated in human bladder carcinomas. A subset of these tumors with poor outcomes produce low levels of FGFR2-IIIb. The synthesis of this receptor de novo in bladder cell lines reduces proliferation in vitro and tumor growth in nude mice. FGFR2-IIIb functions as a tumor suppressor, consistent with the differentiation-inducing capacities of FGF receptors in the suprabasal cells of the skin. FGFR2-IIIb signaling may be involved in the maintenance of E-cadherin, the prototype epithelial adhesion molecule, which is only downregulated in a fraction of tumors with low FGFR2-IIIb synthesis. Human bladder tumors may also activate autocrine loops such as that for EGFR and their ligands, as already demonstrated for murine bladder tumors. Therefore, our results suggest that multifunctional growth factors and their receptors are involved in cell proliferation and epithelial cell plasticity, acting either as positive or negative regulators of tumor progression. The effect on the morphological transition is also clearly relevant to the mechanism governing dissemination and the formation of micrometastatic tumor cells. The extrapolation of these discoveries to human carcinomas should provide markers facilitating the more accurate prediction of the biological behavior of a given tumor and identify clinically and pathologically significant parameters. The identification of critical changes in the growth factor pathways involved in tumor progression will not only provide insight into the genetic and molecular basis of this process, but should also identify targets for new therapies.