Abstract
During CNS development, combinatorial expression of transcription factors controls neuronal subtype identity and subsequent axonal trajectory. Regulatory genes designating the routing of retinal ganglion cell (RGC) axons at the optic chiasm to the appropriate hemisphere, a pattern critical for proper binocular vision, have not been identified. Here, we show that the zinc finger transcription factor Zic2, a vertebrate homolog of the Drosophila gene odd-paired, is expressed in RGCs with an uncrossed trajectory during the period when this subpopulation grows from the ventrotemporal retina toward the optic chiasm. Loss- and gain-of-function analyses indicate that Zic2 is necessary and sufficient to regulate RGC axon repulsion by cues at the optic chiasm midline. Moreover, Zic2 expression reflects the extent of binocularity in different species, suggesting that Zic2 is an evolutionarily conserved determinant of RGCs that project ipsilaterally. These data provide evidence for transcriptional coding of axon pathfinding at the midline.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Axons / metabolism
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Brain / embryology
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Bromodeoxyuridine / pharmacology
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Cell Line
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Down-Regulation
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Drosophila Proteins / metabolism
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Fluorescent Dyes / pharmacology
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Genotype
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Green Fluorescent Proteins
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Homeodomain Proteins / metabolism
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Humans
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Immunoblotting
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Immunohistochemistry
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Luminescent Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microscopy, Fluorescence
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Mitosis
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Models, Biological
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Nuclear Proteins
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Optic Nerve / metabolism
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Retina / anatomy & histology
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Retina / embryology
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Retina / metabolism
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Retina / physiology*
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Sindbis Virus / genetics
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Time Factors
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Transcription, Genetic
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Transfection
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Vision, Ocular / physiology*
Substances
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Drosophila Proteins
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Fluorescent Dyes
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Homeodomain Proteins
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Luminescent Proteins
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Nuclear Proteins
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Opa protein, Drosophila
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Transcription Factors
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ZIC2 protein, human
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Zic2 protein, mouse
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Green Fluorescent Proteins
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Bromodeoxyuridine