title: Drosophila homolog of the myotonic dystrophy-associated gene, SIX5, is required for muscle and gonad development.
abstract: SIX5 belongs to a family of highly conserved homeodomain transcription factors implicated in development and disease. The mammalian SIX5/SIX4 gene pair is likely to be involved in the development of mesodermal structures. 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. 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. 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.
authors.affiliation: Institute of Cell and Molecular Biology, EH9 3JR, Edinburgh, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Kirby
authors.forename: G M
authors.initials: GM
authors.lastname: Hamilton
authors.forename: D J
authors.initials: DJ
authors.lastname: Finnegan
authors.forename: K J
authors.initials: KJ
authors.lastname: Johnson
authors.forename: A P
authors.initials: AP
authors.lastname: Jarman
mesh_terms: D000818:Animals; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010802:Phylogeny; D012333:RNA, Messenger / Q000096:biosynthesis; D013737:Testis / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C106687:SIX5 protein, human; C434485:Six4 protein, Drosophila; D014157:Transcription Factors