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

Séverine Marcos, Monica González-Lázaro, Leonardo Beccari, Laura Carramolino, Maria Jesus Martin-Bermejo, Oana Amarie, Daniel Mateos San Martı́n, Carlos Torroja, Ozren Bogdanović, Roisin Doohan, Oliver Puk, Martin Hrabĕ de Angelis, Jochen Graw, Jose Luis Gomez-Skarmeta, Fernando Casares, Miguel Torres, Paola Bovolenta

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Microphthalmos is a rare congenital anomaly characterized by reduced eye size and visual deficits of variable degree. Sporadic and hereditary microphthalmos have been associated with 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, which encodes a transcription factor with evolutionarily conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment in adultmice. By combining analysis of Meis1 loss-offunction and conditional Meis1 functional rescue with ChIP-seq and RNA-seq approaches we show that, in contrast to its preferential association with Hox-Pbx BSs in the trunk, Meis1 binds to Hox/Pbxindependent 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 of the Notch signaling 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 propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations.

Original languageEnglish
Pages (from-to)3009-3020
Number of pages12
JournalDevelopment (Cambridge)
Issue number17
StatePublished - 1 Sep 2015
Externally publishedYes


  • Developmental disorders
  • Microphthalmia
  • Mouse
  • Notch signaling
  • Patterning
  • TALE transcription factors


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