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

Kirby, R.J., Hamilton, G.M., Finnegan, D.J., Johnson, K.J. and Jarman, A.P. (2001) Drosophila homolog of the myotonic dystrophy-associated gene, SIX5, is required for muscle and gonad development. Current Biology, 11, pp. 1044-1049. (doi: 10.1016/S0960-9822(01)00319-0)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hamilton, Dr Graham
• Authors: Kirby, R.J., Hamilton, G.M., Finnegan, D.J., Johnson, K.J., and Jarman, A.P.
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Current Biology