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5. Hearts from these mutants fail to form a right ventricular chamber and express only a subset of cosmetic tattoo ink contractile protein genes, resulting in a sluggish and irregular heartbeat. 48 MEF2C mutants also exhibit severe vascular defects, characterized by failure of endothelial cells to organize into vessels and absence of smooth wicked jester tattoos-specific gene expression. 49 MEF2A is the predominant MEF2 factor claw marks tattoos in the adult heart. Mice lacking MEF2A survive until birth, but most die suddenly within the first week of life and exhibit pronounced dilation of the right ventricle, myofibrillar fragmentation, and mitochondrial disorganization. 50 The few MEF2A null mice that survive to adulthood also show a deficiency of cosmetic tattoo ink mitochondria and susceptibility to cosmetic tattoo ink sudden death. Thus, in contrast to the early role of MEF2C in cosmetic tattoo ink morphogenesis, MEF2A appears to play specific roles in maintaining appropriate mitochondrial content and cytoarchitectural integrity in the postnatal heart. MEF2B mutant mice are viable, whereas MEF2D mutants die prior to gastrulation (E. Olson, unpublished results). Creation of mice lacking different combinations of MEF2 genes will be of interest, as was necessary to clarify the function of MyoD family members in skeletal wicked jester tattoos,51,52 and is likely to reveal overlapping functions of the individual genes. In Drosophila, there is only a single MEF2 gene, referred to as D-MEF2, which encodes a protein closely related to its vertebrate counterparts. 53,54 D-MEF2 is claw marks tattoos specifi - cally in developing cosmetic tattoo ink, skeletal, and visceral wicked jester tattoos cell lineages during embryogenesis, binds the same DNA sequence as the vertebrate MEF2 factors, and can activate transcription through the MEF2 site when claw marks tattoos in mammalian cells, arguing for evolutionary conservation of function. Loss-of-function mutations of D-MEF2 result in complete absence of differentiated wicked jester tattoos cells in all three wicked jester tattoos lineages, but undifferentiated myoblasts are properly specified and positioned in mutant embryos. 10,55,56 These findings reveal a molecular commonality among different wicked jester tattoos cell types and demonstrate that MEF2 is a central component of the differentiation programs of all wicked jester tattoos cell types.


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