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First published online 15 April 2009
doi: 10.1242/dev.033290

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Neuroepithelial cells require fucosylated glycans to guide the migration of vagus motor neuron progenitors in the developing zebrafish hindbrain

Shinya Ohata^1,*, Shigeharu Kinoshita^1,2,*, Ryo Aoki^1,3, Hideomi Tanaka^1,, Hironori Wada^1,, Sachiko Tsuruoka-Kinoshita^1,4, Takashi Tsuboi³, Shugo Watabe² and Hitoshi Okamoto^1,

¹ Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
² Laboratory of Aquatic Molecular Biology and Biotechnology, Graduate School of Agricultural and Life Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
³ Department of Life Sciences, Graduate School of Arts and Sciences, the University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
⁴ Research Resource Center, RIKEN BSI, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Author for correspondence (e-mail: hitoshi{at}brain.riken.jp)

Accepted 4 March 2009

The molecular mechanisms by which neurons migrate and accumulate to form the neural layers and nuclei remain unclear. The formation of vagus motor nuclei in zebrafish embryos is an ideal model system in which to address this issue because of the transparency of the embryos and the availability of established genetic and molecular biological techniques. To determine the genes required for the formation of the vagus motor nuclei, we performed N-ethyl-N-nitrosourea-based mutant screening using a zebrafish line that expresses green fluorescent protein in the motor neurons. In wild-type embryos, the vagus motor neuron progenitors are born in the ventral ventricular zone, then migrate tangentially in the dorsolateral direction, forming the nuclei. However, in towhead (twd^rw685) mutant embryos, the vagus motor neuron progenitors stray medially away from the normal migratory pathway and fail to stop in the right location. The twd^rw685 mutant has a defect in the GDP-mannose 4,6 dehydratase (gmds) gene, which encodes a key enzyme in the fucosylation pathway. Levels of fucosylated glycans were markedly and specifically reduced in twd^rw685 mutant embryos. Cell transplantation analysis revealed that GMDS is not essential in the vagus motor neuron progenitors for correct formation of the vagus motor nuclei, but is required in the neuroepithelial cells that surround the progenitors. Together, these findings suggest that fucosylated glycans expressed in neuroepithelial cells are required to guide the migration of vagus motor neuron progenitors.

Key words: Fucosylation, GMDS, Neuroepithelial cells, Neural migration, Vagus motor neurons, Zebrafish

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