Spatially and temporally controlled gene expression, including transcription, several mRNA processing steps, and the export of mature mRNA to the cytoplasm, is essential for developmental processes. It is well known that RNA helicases of the DExD/H-box protein family are involved in these gene expression processes, including transcription, pre-mRNA splicing, and rRNA biogenesis. Although one DExD/H-box protein, Prp5, a homologue of vertebrate Ddx46, has been shown to play important roles in pre-mRNA splicing in yeast, the in vivo function of Ddx46 remains to be fully elucidated in metazoans. In this study, we isolated zebrafish morendo (mor), a mutant that shows developmental defects in the digestive organs and brain, and found that it encodes Ddx46. The Ddx46 transcript is maternally supplied, and as development proceeds in zebrafish larvae, its ubiquitous expression gradually becomes restricted to those organs. The results of whole-mount in situ hybridization showed that the expression of various molecular markers in these organs is considerably reduced in the Ddx46 mutant. Furthermore, splicing status analysis with RT-PCR revealed unspliced forms of mRNAs in the digestive organ and brain tissues of the Ddx46 mutant, suggesting that Ddx46 may be required for pre-mRNA splicing during zebrafish development. Therefore, our results suggest a model in which zebrafish Ddx46 is required for the development of the digestive organs and brain, possibly through the control of pre-mRNA splicing.
BackgroundMedial tibial stress syndrome (MTSS) is one of the most common causes of exercise-related leg pain in runners. Because stopping training due to pain from MTSS could decrease the athlete’s competitiveness, it is necessary to construct MTSS prevention and treatment programs. However, the effect of running, which is believed to cause MTSS, on shear elastic modulus of the posterior lower leg is unclear. Therefore, the purpose of this study was to investigate the effect of 30 min of running on shear elastic modulus of the posterior lower leg in healthy subjects.MethodsTwenty healthy males volunteered to participate in this study (age, 20.9 ± 0.6 y; height, 169.6 ± 4.5 cm; weight, 62.6 ± 5.2 kg). The shear elastic modulus of the posterior lower leg was measured using ultrasonic shear wave elastography before and immediately after a 30-min running task.ResultsShear elastic moduli of the flexor digitorum longus and tibialis posterior were significantly increased after 30 min running task. However, there were no significant changes in shear elastic moduli of the lateral gastrocnemius, medial gastrocnemius, peroneus longus and peroneus brevis.ConclusionThe results suggested that the increases in shear elastic moduli of flexor digitorum longus and tibialis posterior after running could be a risk factor for running-related MTSS development.
Balanced and precisely controlled processes between self-renewal and differentiation of hematopoietic stem cells (HSCs) into all blood lineages are critical for vertebrate definitive hematopoiesis. However, the molecular mechanisms underlying the maintenance and differentiation of HSCs have not been fully elucidated. Here, we show that zebrafish Ddx46, encoding a DEAD-box RNA helicase, is expressed in HSCs of the caudal hematopoietic tissue (CHT). The number of HSCs expressing the molecular markers cmyb or T-cell acute lymphocytic leukemia 1 (tal1) was markedly reduced in Ddx46 mutants. However, massive cell death of HSCs was not detected, and proliferation of HSCs was normal in the CHT of the mutants at 48 h postfertilization. We found that myelopoiesis occurred, but erythropoiesis and lymphopoiesis were suppressed, in Ddx46 mutants. Consistent with these results, the expression of spi1, encoding a regulator of myeloid development, was maintained, but the expression of gata1a, encoding a regulator of erythrocyte development, was downregulated in the mutants. Taken together, our results provide the first genetic evidence that zebrafish Ddx46 is required for the multilineage differentiation of HSCs during development, through the regulation of specific gene expressions.
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