English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/129593
Título

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

AutorMarcos, Severine; Beccari, Leonardo; Martín-Bermejo, María Jesús; Bogdanovic, Ozren ; Gómez-Skarmeta, José Luis ; Casares, Fernando ; Torres, Miguel; Bovolenta, Paola
Palabras claveMouse
Microphthalmia
TALE transcription factors
Developmental disorders
Notch signaling
Patterning
Fecha de publicación2015
EditorCompany of Biologists
CitaciónDevelopment 142(17): 3009-3020 (2015)
ResumenMicrophthalmos 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.
Descripciónet al.
URIhttp://hdl.handle.net/10261/129593
DOI10.1242/dev.122176
Identificadoresdoi: 10.1242/dev.122176
e-issn: 1477-9129
issn: 0950-1991
Aparece en las colecciones: (CBM) Artículos
(CABD) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.