The Retinal Homeobox (Rx) gene is necessary for retinal regeneration

• Published in: Developmental biology Vol. 353; no. 1; pp. 10 - 18
• Main Authors: Martinez-De Luna, Reyna I., Kelly, Lisa E., El-Hodiri, Heithem M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2011
• Subjects: Animals; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; eyes; Gene Expression Regulation, Developmental; genes; genetic markers; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Larva - physiology; Regeneration; resection; Retina - cytology; Retina - physiology; Retinal Homeobox; Retinal progenitor cells; shRNA; stem cells; Stem Cells - physiology; tadpoles; Transcription Factors - genetics; Transcription Factors - metabolism; Transdifferentiation; Transgenes; vertebrates; Xenopus laevis; Xenopus laevis - embryology; Regeneration; Retinal Homeobox; Retinal progenitor cells; shRNA; Transdifferentiation
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2011.02.008

The Retinal Homeobox (Rx) gene is essential for vertebrate eye development. Rx function is required for the specification and maintenance of retinal progenitor cells (RPCs). Loss of Rx function leads to a lack of eye development in a variety of species. Here we show that Rx function is also necessary during retinal regeneration. We performed a thorough characterization of retinal regeneration after partial retinal resection in pre-metamorphic Xenopus laevis. We show that after injury the wound is repopulated with retinal progenitor cells (RPCs) that express Rx and other RPC marker genes. We used an shRNA-based approach to specifically silence Rx expression in vivo in tadpoles. We found that loss of Rx function results in impaired retinal regeneration, including defects in the cells that repopulate the wound and the RPE at the wound site. We show that the regeneration defects can be rescued by provision of exogenous Rx. These results demonstrate for the first time that Rx, in addition to being essential during retinal development, also functions during retinal regeneration.
► In Xenopus laevis, retinal regeneration is essentially complete after 30days. ► Retinal progenitor cells form in the wounded area during regeneration. ► Progenitor cells in the regenerate are arranged as in the ciliary marginal zone. ► Knockdown of Rx gene expression disrupts retinal regeneration in Xenopus.