Corson and coworkers investigated fibrillin-3 expression in lung, blood vessels and kidney at later stages of development (20C21st GW) compared to the developmental stages in the present study (6C12th GW). Fibrillin-3 was found spatially expressed in perichondrium, perineurium, perimysium, skin, developing bronchi, glomeruli, pancreas, kidney, heart and testis and at the prospective basement membranes in developing epithelia and endothelia. Double immunohistochemical analyses showed that all fibrillins are globally expressed in the same organs, with a number of differences around the tissue level in cartilage, perichondrium and developing bronchi. These results suggest that fibrillin-3, compared to the other fibrillins, fulfills both overlapping and distinct functions in human development. earlier than the single homozygous null mice with a poorly developed aortic media suggesting functional cooperation of both fibrillins in the development of the aortic matrix (Carta et al., 2006). The absence of fibrillin-1 in lung development leads to failure of distal alveolar septation mediated by elevated TGF- signaling (Neptune et al., 2003). Treatment with fibrillin-2 antisense oligonucleotides induced dysmorphogenesis of rat lung explants (Yang et al., 1999). It remains to be established whether the functions of fibrillin-1 and -2 in lung development are overlapping or distinct. Further evidence for overlapping as well as distinct functions of fibrillin-1 and -2 in development stems from Doxifluridine their involvement in genetic disorders. Doxifluridine Mutations in fibrillin-1 lead to the Marfan syndrome (MFS) characterized by cardinal symptoms in the cardiovascular, skeletal and ocular systems including progressive aortic root enlargement, dolichostenomelia, scoliosis and ectopia lentis (Robinson et al., 2006). Mutations in fibrillin-2 on the other hand give rise to congenital contractural arachnodactyly (CCA) with some overlapping skeletal features with MFS (Frederic et al., 2009). In contrast to MFS, individuals with CCA are characterized by joint contractures and abnormally shaped ears, whereas cardiovascular and Doxifluridine ocular manifestations are usually absent (Viljoen, 1994). The third fibrillin family member, fibrillin-3, was relatively recently discovered and has not been extensively studied. The cDNA coding for fibrillin-3 has first been isolated from human fetal brain (Nagase et al., 2001). Corson and coworkers subsequently found that fibrillin-3, similar to fibrillin-2, is mainly expressed during embryonic development (Corson et al., 2004). Syk Interestingly, the fibrillin-3 gene is not expressed in rodents, although it is usually expressed in many other organisms including primates, cow, sheep, doggie, swine, chick, zebrafish as well as others (Corson et al., 2004). Based on a small set of analyses using indirect immunofluorescence labeling, the fibrillin-3 protein is usually expressed in some human, chick and bovine connective tissues including fetal lung, kidney, skin, muscle and perichondrium (Corson et al., 2004). Around the functional level, fibrillin-3 shares some similarities with the other fibrillin isoforms. The C-terminal half of fibrillin-3 multimerizes and strongly interacts with fibronectin, similar to the C-terminal halves Doxifluridine of fibrillin-1 and -2 (Sabatier et al., 2009). Ultrastructural immunolocalization exhibited association of fibrillin-3 with microfibrils in the perichondrium both in the presence and in the absence of elastic fibers demonstrating that this functional entity of fibrillin-3 is the 10C12 nm in diameter microfibril (Corson et al., 2004). The gene Doxifluridine for fibrillin-3, located on chromosome 19, was originally suggested as a candidate gene for recessive Weill-Marchesani syndrome (Corson et al., 2004). However, subsequently mutations leading to recessive Weill-Marchesani syndrome were identified in ADAMTS10 (Dagoneau et al., 2004). Linkage and immunohistochemical analyses strongly suggests a role for fibrillin-3 in the pathogenesis of polycystic ovary syndrome (Urbanek et al., 2005; Stewart et al., 2006; Ewens et al., 2010; Jordan et al., 2010). Functional single nucleotide polymorphism analysis, however, argued against this possibility (Prodoehl et al., 2009). It is clear that fibrillin-3, like fibrillin-2, is usually a developmentally expressed isoform of the fibrillin family, however, it remains to be established whether fibrillin-3 represents a redundant protein or whether it confers specific,.
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