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首页> 外文期刊>Development >Hand, an evolutionarily conserved bHLH transcription factor required for Drosophila cardiogenesis and hematopoiesis.
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Hand, an evolutionarily conserved bHLH transcription factor required for Drosophila cardiogenesis and hematopoiesis.

机译:手,果蝇心脏发生和造血所必需的进化保守的bHLH转录因子。

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摘要

The Hand gene family encodes highly conserved basic helix-loop-helix (bHLH) transcription factors that play crucial roles in cardiac and vascular development in vertebrates. In Drosophila, a single Hand gene is expressed in the three major cell types that comprise the circulatory system: cardioblasts, pericardial nephrocytes and lymph gland hematopoietic progenitors, but its function has not been determined. Here we show that Drosophila Hand functions as a potent transcriptional activator, and converting it into a repressor blocks heart and lymph gland formation. Disruption of Hand function by homologous recombination also results in profound cardiac defects that include hypoplastic myocardium and a deficiency of pericardial and lymph gland hematopoietic cells, accompanied by cardiac apoptosis. Targeted expression of Hand in the heart completely rescued the lethality of Hand mutants, and cardiac expression of a human HAND gene, or the caspase inhibitor P35, partially rescued the cardiac and lymph gland phenotypes. These findings demonstrate evolutionarily conserved functions of HAND transcription factors in Drosophila and mammalian cardiogenesis, and reveal a previously unrecognized requirement of Hand genes in hematopoiesis.
机译:Hand基因家族编码高度保守的基本螺旋-环-螺旋(bHLH)转录因子,这些因子在脊椎动物的心脏和血管发育中起关键作用。在果蝇中,单一的Hand基因在构成循环系统的三种主要细胞类型中表达:成心脏细胞,心包肾细胞和淋巴造血祖细胞,但其功能尚未确定。在这里,我们显示果蝇的手起有效的转录激活剂的作用,并将其转化为阻遏物,可阻止心脏和淋巴腺的形成。同源重组破坏手功能也会导致严重的心脏缺陷,包括心肌发育不良,心包和淋巴腺造血细胞缺乏,并伴有心脏凋亡。 Hand在心脏中的靶向表达完全挽救了Hand突变体的致死性,而人类HAND基因或caspase抑制剂P35的心脏表达则部分挽救了心脏和淋巴腺的表型。这些发现证明了果蝇中HAND转录因子在进化上的保守功能和哺乳动物的心脏发生,并揭示了造血过程中Hand基因先前未被认识的需求。

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