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First published online February 9, 2007
doi: 10.1242/10.1242/dev.02782

Development 134, 979-988 (2007)
Published by The Company of Biologists 2007
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Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation

Huizhe Huang1,*, Fu-I Lu2,*, Shunji Jia1,*, Shu Meng1, Ying Cao1, Yeqi Wang1, Weiping Ma3, Kun Yin1, Zilong Wen3, Jingrong Peng3, Christine Thisse2, Bernard Thisse2,{dagger} and Anming Meng1,{dagger}

1 State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
2 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1, rue Laurent Fries, BP10142, 67404 Illkirch Cedex, France.
3 Institute of Molecular and Cell Biology, Proteos, 138673, Singapore.

{dagger} Authors for correspondence (e-mail: thisse{at}titus.u-strasbg.fr; mengam{at}mail.tsinghua.edu.cn)

Accepted 14 December 2006

Angiomotin (Amot), the founding member of the Motin family, is involved in angiogenesis by regulating endothelial cell motility, and is required for visceral endoderm movement in mice. However, little is known about biological functions of the other two members of the Motin family, Angiomotin-like1 (Amotl1) and Angiomotin-like2 (Amotl2). Here, we have identified zebrafish amotl2 as an Fgf-responsive gene. Zebrafish amotl2 is expressed maternally and in restricted cell types zygotically. Knockdown of amotl2 expression delays epiboly and impairs convergence and extension movement, and amotl2-deficient cells in mosaic embryos fail to migrate properly. This coincides with loss of membrane protrusions and disorder of F-actin. Amotl2 partially co-localizes with RhoB-or EEA1-positive endosomes and the non-receptor tyrosine kinase c-Src. We further demonstrate that Amotl2 interacts preferentially with and facilitates outward translocation of the phosphorylated c-Src, which may in turn regulate the membrane architecture. These data provide the first evidence that amotl2 is essential for cell movements in vertebrate embryos.

Key words: Zebrafish, Epiboly, Convergent extension, c-Src, Angiomotin-like2




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