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Marcos, S.* ; González-Lázaro, M.* ; Beccari, L.* ; Carramolino, L.* ; Martin-Bermejo, M.J.* ; Amarie, O.V. ; Martín, D.M.* ; Torroja, C.* ; Bogdanović, O.* ; Doohan, R.* ; Puk, O. ; Hrabě de Angelis, M. ; Graw, J. ; Gómez-Skarmeta, J.L.* ; Casares, F.* ; Torres, M.* ; Bovolenta, P.*

Meis1 coordinates a network of genes implicated in eye development and microphthalmia.

Development 142, 3009-3020 (2015)
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Open Access Green
Microphthalmos is a rare congenital anomaly characterized by reduced eye size and visual deficits of variable degrees. Sporadic and hereditary microphthalmos has been associated to heterozygous mutations in genes fundamental for eye development. Yet, many cases are idiopathic or await the identification of molecular causes. Here we show that haploinsufficiency of Meis1, a transcription factor with an evolutionary conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment, in adult mice. By combining the analysis of Meis1 loss-of-function and conditional Meis1 functional rescue with ChIP-seq and RNA-seq approaches we show that, in contrast to Meis1 preferential association with Hox-Pbx binding sites in the trunk, Meis1 binds to Hox/Pbx-independent sites during optic cup development. In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components the Notch signalling pathway. In addition, Meis1 is required for eye patterning by controlling a set of eye territory-specific transcription factors, so that in Meis1(-/-) embryos boundaries among the different eye territories are shifted or blurred. We thus propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, itself representing an additional candidate for syndromic cases of these ocular malformations.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Developmental Disorders ; Microphthalmia ; Mouse ; Notch Signaling ; Patterning ; Tale Transcription Factors
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Quellenangaben Band: 142, Heft: 17, Seiten: 3009-3020 Artikelnummer: , Supplement: ,
Verlag Company of Biologists
Begutachtungsstatus Peer reviewed