Meis1 coordinates a network of genes implicated in eye development and microphthalmia
| Autor: | Fernando Casares, Oliver Puk, Oana V. Amarie, Ozren Bogdanovic, Paola Bovolenta, Miguel Torres, Martin Hrabě de Angelis, Séverine Marcos, María Jesús Martín-Bermejo, José Luis Gómez-Skarmeta, Laura Carramolino, Mónica González-Lázaro, Carlos Torroja, Leonardo Beccari, Daniel Mateos San Martín, Jochen Graw, Roisin Doohan |
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| Přispěvatelé: | Fundación Ramón Areces, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Australian Research Council, Fundación Pro CNIC, Federación Española de Enfermedades Raras, Centro de Investigación Biomédica en Red Enfermedades Raras (España), Comunidad de Madrid, Junta de Andalucía |
| Rok vydání: | 2015 |
| Předmět: |
Aging
Chromatin Immunoprecipitation genetic structures Mouse Neurogenesis Molecular Sequence Data Notch signaling pathway Apoptosis Haploinsufficiency Biology Eye Microphthalmia Reduced eye TALE transcription factors Mice medicine Animals Humans Microphthalmos Gene Regulatory Networks Hox gene Myeloid Ecotropic Viral Integration Site 1 Protein Molecular Biology Transcription factor Notch signaling Genetics Homeodomain Proteins Binding Sites Base Sequence Receptors Notch Developmental disorders medicine.disease Embryo Mammalian eye diseases Hematopoiesis Neoplasm Proteins Patterning Enhancer Elements Genetic Developmental Disorders Notch Signaling Tale Transcription Factors Eye development Blood Vessels sense organs Developmental Biology Protein Binding Signal Transduction |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Development 142, 3009-3020 (2015) |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | et al. 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. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2010-16031; BFU2013-43213-P, supported by FEDER Funds], the CIBERER, Instituto de Salud Carlos III (ISCIII) to P.B. and an Institutional Grant from the Fundación Ramon Areces; by MINECO [BFU2012-31086] and ISCIII [RD12/0019/0005] to M.T.; by Comunidad Autonoma de Madrid (CAM) [S2010/BMD-2315] to P.B. and M.T.; by MINECO [BFU2013-41322-P] and Andalusian Government [BIO-396] to J.L.G.-S.; and by MINECO [BFU2014-55738-REDT] to P.B., J.L.G.-S. and F.C. M.G.-L. was supported by a grant from the CONACyT. O.B. is supported by an Australian Research Council Discovery Early Career Researcher Award-DECRA [DE140101962]. The CNIC is supported by MINECO and the Pro-CNIC Foundation. |
| Databáze: | OpenAIRE |
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