title: Brief report: Rx1 defines retinal precursor identity by repressing alternative fates through the activation of TLE2 and Hes4.
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.
authors.affiliation: Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, Pisa, Italy; Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Giannaccini
authors.forename: Guido
authors.initials: G
authors.lastname: Giudetti
authors.forename: Daniele
authors.initials: D
authors.lastname: Biasci
authors.forename: Sara
authors.initials: S
authors.lastname: Mariotti
authors.forename: Davide
authors.initials: D
authors.lastname: Martini
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barsacchi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Andreazzoli
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D012097:Repressor Proteins / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D005136:Eye Proteins; C524416:Rax protein, Xenopus; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins
keywords: Multipotency; Retina; Transcription factors; Xenopus