Role of adenylate cyclase 1 in retinofugal map development

Authors

  • Onkar S. Dhande,

    1. Department of Neurobiology, Yale University, New Haven, Connecticut 06510
    2. Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030
    Current affiliation:
    1. Neurosciences Department, School of Medicine, University of California, San Diego, La Jolla, CA 92093
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  • Shivani Bhatt,

    1. Department of Neurobiology, Yale University, New Haven, Connecticut 06510
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  • Anastacia Anishchenko,

    1. Department of Molecular and Cell Biology and Helen Willis Neuroscience Institute, University of California at Berkeley, Berkeley, California 94720
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  • Justin Elstrott,

    1. Department of Molecular and Cell Biology and Helen Willis Neuroscience Institute, University of California at Berkeley, Berkeley, California 94720
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  • Takuji Iwasato,

    1. Laboratory for Behavioral Genetics, RIKEN Brain Science Institute (BSI), Saitama 351-0198, Japan
    Current affiliation:
    1. National Institute of Genetics, Shizuoka 411-8540, Japan
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  • Eric C. Swindell,

    1. Deparment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030
    Current affiliation:
    1. Department of Pediatrics, University of Texas-Houston Medical School, Houston, TX 77030
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  • Hong-Ping Xu,

    1. Department of Neurobiology, Yale University, New Haven, Connecticut 06510
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  • Milan Jamrich,

    1. Deparment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030
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  • Shigeyoshi Itohara,

    1. Laboratory for Behavioral Genetics, RIKEN Brain Science Institute (BSI), Saitama 351-0198, Japan
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  • Marla B. Feller,

    1. Department of Molecular and Cell Biology and Helen Willis Neuroscience Institute, University of California at Berkeley, Berkeley, California 94720
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  • Michael C. Crair

    Corresponding author
    1. Department of Neurobiology, Yale University, New Haven, Connecticut 06510
    • 333 Cedar St., SHM B301; Yale University School of Medicine; New Haven, CT 06510
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Abstract

The development of topographic maps of the sensory periphery is sensitive to the disruption of adenylate cyclase 1 (AC1) signaling. AC1 catalyzes the production of cAMP in a Ca2+/calmodulin-dependent manner, and AC1 mutant mice (AC1−/−) have disordered visual and somatotopic maps. However, the broad expression of AC1 in the brain and the promiscuous nature of cAMP signaling have frustrated attempts to determine the underlying mechanism of AC1-dependent map development. In the mammalian visual system, the initial coarse targeting of retinal ganglion cell (RGC) projections to the superior colliculus (SC) and lateral geniculate nucleus (LGN) is guided by molecular cues, and the subsequent refinement of these crude projections occurs via an activity-dependent process that depends on spontaneous retinal waves. Here, we show that AC1−/− mice have normal retinal waves but disrupted map refinement. We demonstrate that AC1 is required for the emergence of dense and focused termination zones and elimination of inaccurately targeted collaterals at the level of individual retinofugal arbors. Conditional deletion of AC1 in the retina recapitulates map defects, indicating that the locus of map disruptions in the SC and dorsal LGN of AC1−/− mice is presynaptic. Finally, map defects in mice without AC1 and disrupted retinal waves (AC1−/−;β2−/− double KO mice) are no worse than those in mice lacking only β2−/−, but loss of AC1 occludes map recovery in β2−/− mice during the second postnatal week. These results suggest that AC1 in RGC axons mediates the development of retinotopy and eye-specific segregation in the SC and dorsal LGN. J. Comp. Neurol. 520:1562–1583, 2012. © 2011 Wiley Periodicals, Inc.

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