RESUMO
Some of the earliest axon pathways to form in the vertebrate forebrain are established as commissural and retinal axons cross the midline of the diencephalon and telencephalon. To better understand axon guidance in the forebrain, we characterized the zebrafish belladonna (bel) mutation, which disrupts commissural and retinal axon guidance in the forebrain. Using a positional cloning strategy, we determined that the bel locus encodes zebrafish Lhx2, a lim-homeodomain transcription factor expressed in the brain, eye and fin buds. We show that bel(Ihx2) function is required for patterning in the ventral forebrain and eye, and that loss of bel function leads to alterations in regulatory gene expression, perturbations in axon guidance factors, and the absence of an optic chiasm and forebrain commissures. Our analysis reveals new roles for Ihx2 in midline axon guidance, forebrain patterning and eye morphogenesis.
Assuntos
Axônios/fisiologia , Padronização Corporal , Olho/embriologia , Prosencéfalo/embriologia , Proteínas de Peixe-Zebra/fisiologia , Peixe-Zebra/embriologia , Sequência de Aminoácidos , Animais , Proliferação de Células , Diencéfalo/embriologia , Diencéfalo/metabolismo , Olho/citologia , Fatores de Crescimento de Fibroblastos/metabolismo , Proteínas com Homeodomínio LIM , Dados de Sequência Molecular , Morfogênese , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Neuroglia/fisiologia , Transdução de Sinais , Telencéfalo/embriologia , Telencéfalo/metabolismo , Fatores de Transcrição , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genéticaRESUMO
Genetic screens in zebrafish have identified a large number of mutations that affect neural connectivity in the developing visual system. These mutants define genes essential for accurate retinal axon guidance in the eye and brain and the characterization of these mutants is helping to define the cellular and molecular mechanisms that guide axons in the vertebrate embryo. The combination of zebrafish genetic and embryological approaches promises to greatly increase our understanding of how multiple guidance mechanisms establish the complex neural interconnectivity of the vertebrate brain.
