title: Drosophila eye developmental defect caused by elevation of the activity of the LIM-homeodomain protein, Lmx1a, requires its association with the Co-activator Chip.
abstract: The LIM-homeodomain (LIM-HD) family member Lmx1a has been successfully used to induce dopaminergic neurons from other cell types, thus showing significant implications in replacement therapies of Parkinson's disease, but the underlying mechanism remains elusive. In this study, we used Drosophila eye as a model system to investigate how forced expression of dLmx1a, the fly homolog of human Lmx1a, alters cell identify. We found that ectopic expression of dLmx1a suppresses the formation of Drosophila eye tissue and identified the LIM and HD as two essential domains. dLmx1a requires and physically binds to Chip, a well-known cofactor of LIM-HD proteins. Chip connects two dLmx1a proteins to form a functional tetrameric complex. In addition, we provide evidence showing that dLmx1a expression results in the suppression of two retina determination gene eyes absent (eya) and string (stg). Taken together, our findings identified Chip as a novel partner of dLmx1a to alter cell differentiation in Drosophila eye through repressing eya and stg expression, and provide an animal model for further understanding the molecular mechanism whereby Lmx1a determines cell fate.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Runan
authors.initials: R
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Liangchang
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yuanpei
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China. Electronic address: wusa@nankai.edu.cn.
authors.forename: Shian
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009799:Ocular Physiological Phenomena; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C108740:Chi protein, Drosophila; D029721:Drosophila Proteins; D005136:Eye Proteins; D060850:LIM-Homeodomain Proteins; C000608147:Lmx1a protein, Drosophila; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: Chip; Drosophila; Eya; LIM-HD; dLmx1a