Drosophila homolog of the myotonic dystrophy-associated gene, SIX5, is required for muscle and gonad development

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• 作者：Ruth J. Kirby ; Graham M. Hamilton ; David J. Finnegan ; Keith J. Johnson ; Andrew P. Jarman
• 关键词：Biochemistry ; Cell Biology ; Genetics
• 刊名：Current Biology
• 出版年：2001
• 出版时间：10 July 2001
• 年：2001
• 卷：11
• 期：13
• 页码：1044-1049
• 全文大小：291 K

文摘

SIX5 belongs to a family of highly conserved homeodomain transcription factors implicated in development and disease [1, 2 and 3]. The mammalian SIX5/SIX4 gene pair is likely to be involved in the development of mesodermal structures [4, 5 and 6]. Moreover, a variety of data have implicated human SIX5 dysfunction as a contributor to myotonic dystrophy type 1 (DM1), a condition characterized by a number of pathologies including muscle defects and testicular atrophy [7, 8 and 9]. However, this link remains controversial. Here, we investigate the Drosophila gene, D-Six4, which is the closest homolog to SIX5 of the three Drosophila Six family members [10]. We show by mutant analysis that D-Six4 is required for the normal development of muscle and the mesodermal component of the gonad. Moreover, adult males with defective D-Six4 genes exhibit testicular reduction. We propose that D-Six4 directly or indirectly regulates genes involved in the cell recognition events required for myoblast fusion and the germline:soma interaction. While the exact phenotypic relationship between D-Six4 and SIX4/5 remains to be elucidated, the defects in D-Six4 mutant flies suggest that human SIX5 should be more strongly considered as being responsible for the muscle wasting and testicular atrophy phenotypes in DM1.