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Development ; 143(22): 4182-4192, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27697904

RESUMO

The Lim domain-binding proteins are key co-factor proteins that assemble with LIM domains of the LMO/LIM-HD family to form functional complexes that regulate cell proliferation and differentiation. Using conditional mutagenesis and comparative phenotypic analysis, we analyze the function of Ldb1 and Ldb2 in mouse retinal development, and demonstrate overlapping and specific functions of both proteins. Ldb1 interacts with Lhx2 in the embryonic retina and both Ldb1 and Ldb2 play a key role in maintaining the pool of retinal progenitor cells. This is accomplished by controlling the expression of the Vsx2 and Rax, and components of the Notch and Hedgehog signaling pathways. Furthermore, the Ldb1/Ldb2-mediated complex is essential for generation of early-born photoreceptors through the regulation of Rax and Crx. Finally, we demonstrate functional redundancy between Ldb1 and Ldb2. Ldb1 can fully compensate the loss of Ldb2 during all phases of retinal development, whereas Ldb2 alone is sufficient to sustain activity of Lhx2 in both early- and late-stage RPCs and in Müller glia. By contrast, loss of Ldb1 disrupts activity of the LIM domain factors in neuronal precursors. An intricate regulatory network exists that is mediated by Ldb1 and Ldb2, and promotes RPC proliferation and multipotency; it also controls specification of mammalian retina cells.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Proteínas com Domínio LIM/fisiologia , Organogênese/genética , Retina/embriologia , Fatores de Transcrição/fisiologia , Animais , Diferenciação Celular/genética , Proliferação de Células/genética , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes/fisiologia , Mamíferos/embriologia , Mamíferos/genética , Camundongos , Camundongos Transgênicos , Retina/citologia , Retina/metabolismo , Células-Tronco/fisiologia
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