Brief Report: Rx1 Defines Retinal Precursor Identity by Repressing Alternative Fates Through the Activation of TLE2 and Hes4

Authors

  • Martina Giannaccini,

    1. Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy
    2. Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, Pisa, Italy
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  • Guido Giudetti,

    1. Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy
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  • Daniele Biasci,

    1. Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy
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  • Sara Mariotti,

    1. Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy
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  • Davide Martini,

    1. Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy
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  • Giuseppina Barsacchi,

    1. Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy
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  • Massimiliano Andreazzoli

    Corresponding author
    1. Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy
    • Correspondence: Massimiliano Andreazzoli, Ph.D., Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa 56127, Italy. Telephone: 39–050-2211485; Fax: 39–050-2211495; e-mail: mandreazzoli@biologia.unipi.it

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  • Author contributions: M.G. and G.G.: conception and design, collection and assembly of data, and data analysis and interpretation; D.B.: data analysis and interpretation; S.M. and D.M.: collection of data, and data analysis and interpretation; G.B.: data analysis and interpretation and financial support; M.A.: conception and design, collection and assembly of data, data analysis and interpretation, financial support, and manuscript writing.

Abstract

The molecular mechanisms underlying the acquisition of retinal precursor identity are scarcely defined. Although the homeobox gene Rx1 (also known as Rax) plays a major role in specifying retinal precursors and maintaining their multipotent state, the involved mechanisms remain to be largely deciphered. Here, following a highthroughput screen for genes regulated by Rx1, we found that this transcription factor specifies the fate of retinal progenitors by repressing genes normally activated in adjacent ectodermal territories. Unexpectedly, we also observed that Rx1, mainly through the activation of the transcriptional repressors TLE2 and Hes4, is necessary and sufficient to inhibit endomesodermal gene expression in retinal precursors of the eye field. In particular, Rx1 knockdown leads retinogenic blastomeres to adopt an endomesodermal fate, indicating a previously undescribed function for Rx1 in preventing the expression of endomesoderm determinants known to inhibit retinal fate. Altogether these data suggest that an essential requirement to establish a retinal precursor identity is the active inhibition of pathways leading to alternative fates. Stem Cells 2013;31:2842–2847

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