Перегляд вихідного коду сторінки What The Heck Is Going On With A-1210477

?8B�CG and data not shown; p?=?0.034, n?=?100). Additionally, skeletal muscle contractions, which were abolished in Rbfox double morphants, were completely restored upon rbfox2 mRNA injection (p?[http://www.selleckchem.com/products/a-1210477.html A-1210477 in vivo] to control embryos (p?=?5?��?10??4, n?=?124) but no different from rates observed in rbfox2 mRNA-injected control embryos ( Fig.?8H; p?=?0.98, n?=?22). As expected, immunohistochemistry revealed that muscle fiber organization was also dramatically restored in rbfox2 mRNA-injected double morphant embryos ( Fig.?9). Labeling of slow and fast muscle fiber components using anti-MHC or Alexa-fluor 488-conjugated phalloidin ( Fig.?9A�CC and D�CI, respectively) showed that both slow and fast muscles appear striated in rbfox2 mRNA-injected double morphant embryos. The persistence of slightly wavy fibers may correlate with the reduced strength, but not frequency, of skeletal muscle contractions observed in these embryos. Together, these data show that splicing, morphological, and physiological defects that arise from rbfox1l- and rbfox2-targeting sbMOs are a specific result of knockdown of Rbfox [http://en.wikipedia.org/wiki/Diglyceride diglyceride] proteins. Our results show that disruption of splicing regulatory proteins in zebrafish embryos can provide new insights into tissue-specific alternative splicing patterns in vivo and their importance for early vertebrate development. More specifically, these studies indicate that Rbfox1l and Rbfox2 regulate partially overlapping networks of alternative splicing events in zebrafish muscle, with individual differences likely due to differential expression of Rbfox1l and/or Rbfox2 in specific cell or tissues, or by recruitment of regulatory co-factors that are unique to either Rbfox protein (Kim et al., 2010). Overall, our experiments demonstrate that conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated [http://www.selleckchem.com/products/ldn193189.html see more] alternative splicing. However, a few muscle-specific Rbfox motif-associated alternative exons were not demonstrably altered by rbfox1l/2 knockdown, indicating that additional splicing factors may be essential in regulation of the muscle alternative splicing program. The immotile and disorganized myofibril phenotype of rbfox1l/rbfox2 double morphants is similar to that of a number of previously characterized zebrafish mutants and morphants. Genes identified in these studies act at multiple levels of myofiber development, affecting the function of specific muscle structural proteins, myofiber assembly and maintenance, and/or muscle fiber connections at the myotendinous junction.