Glycobiology Advance Access published online on November 16, 2006
Glycobiology, doi:10.1093/glycob/cwl069
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Agrin is Required for Posterior Development and Motor Axon Outgrowth and Branching in Embryonic Zebrafish

1 Laboratory of Molecular Genetics, NICHD, NIH, Bethesda, MD 20892
2 Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707
3 Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
4 Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15261
5 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710
To whom correspondence should be addressed: Dr. Gregory J. Cole, Biomedical/Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC 27707, T: 919.530.7028, F: 919.530.7998, e-mail: gcole{at}nccu.edu
Received on October 11, 2006; revised on November 9, 2006; accepted on November 11, 2006
Although recent studies have extended our understanding of agrin's function during development, its function in the CNS is not clearly understood. To begin to address this question, zebrafish agrin was identified and characterized. Zebrafish agrin is expressed in the developing CNS and in non-neural structures such as somites and notochord. In agrin morphant embryos, acetylcholine receptor (AChR) cluster number and size on muscle fibers at the choice point were unaffected, while AChR clusters on muscle fibers in the dorsal and ventral regions of the myotome were reduced or absent. Defects in axon outgrowth by primary motor neurons, subpopulations of branchiomotor neurons, and by Rohon-Beard sensory neurons were also observed, which included truncation of axons and increased branching of motor axons. Moreover, agrin morphants exhibit significantly inhibited tail development in a dose-dependent manner, as well as defects in the formation of the midbrain-hindbrain boundary and reduced size of eyes and otic vesicles. Together these results show that agrin plays an important role in both peripheral and central nervous system development, and also modulates posterior development in zebrafish.
Key words: agrin / heparan sulfate proteoglycan / axon outgrowth / zebrafish / posterior development / Fgf / neuromuscular synaptogenesis
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