Glycobiology Advance Access originally published online on November 16, 2006
Glycobiology 2007 17(2):231-247; doi:10.1093/glycob/cwl069
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Agrin is required for posterior development and motor axon outgrowth and branching in embryonic zebrafish
2 Laboratory of Molecular Genetics, NICHD, NIH, Bethesda, MD 20892
3 Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC 27707
4 Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
5 Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15261
6 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710
1 To whom correspondence should be addressed; Tel: +1 919-5307028; Fax: +1 919-5307998; 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 central nervous system (CNS) is not clearly understood. To address this question, zebrafish agrin was identified and characterized. Zebrafish agrin is expressed in the developing CNS and in nonneural 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, whereas AChR clusters on muscle fibers in the dorsal and ventral regions of the myotome were reduced or absent. Defects in the axon outgrowth by primary motor neurons, subpopulations of branchiomotor neurons, and 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 CNS development and also modulates posterior development in zebrafish.
Key words: agrin / heparan sulfate proteoglycan / axon outgrowth / zebrafish / posterior development / Fgf / neuromuscular synaptogenesis
* These authors contributed equally to this work.
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