KIF3A is a classical member of the kinesin superfamily proteins (KIFs), ubiquitously expressed although predominantly in neural tissues, and which forms a heterotrimeric KIF3 complex with KIF3B or KIF3C and an associated protein, KAP3. To elucidate the function of the kif3A gene in vivo, we made kif3A knockout mice. kif3A−/− embryos displayed severe developmental abnormalities characterized by neural tube degeneration and mesodermal and caudal dysgenesis and died during the midgestational period at ∼10.5 dpc (days post coitum), possibly resulting from cardiovascular insufficiency. Whole mount in situ hybridization of Pax6 revealed a normal pattern while staining by sonic hedgehog (shh) and Brachyury (T) exhibited abnormal patterns in the anterior-posterior (A-P) direction at both mesencephalic and thoracic levels. These results suggest that KIF3A might be involved in mesodermal patterning and in turn neurogenesis.
Left-Right Asymmetry and Kinesin Superfamily Protein KIF3A: New Insights in Determination of Laterality and Mesoderm Induction by kif3A−/− Mice Analysis
Address correspondence to Nobutaka Hirokawa, Department of Cell Biology and Anatomy, University of Tokyo, Graduate School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 Japan. Tel.: 81-3-3812-2111, ext. 3326. Fax: 81-3-5802-8646. E-mail: [email protected]
We should like to express our gratitude to Dr. Toshimichi Yoshida (Mie University, Japan) for the anti-axonemal outer arm dynein antibody (AD2); Dr. Winfield Sale (Emory University, Georgia) for the anti-dynein intermediate chain antibody (IC140); Dr. Hiroshi Hamada (Osaka University, Japan) for the lefty-2 and shh probe; Drs. Yumiko Saga (National Institute of Health Science, Japan) and Bernhard G. Herrmann (Max-Planck Institut für Entwicklungsbiologie, Tübingen, Germany) for the Brachyury probe; Dr. Peter Gruss (Max-Planck Institut für Biophysikalische Chemie, Göttingen, Germany) for the Pax6 probe. We appreciate Dr. Mika Karasawa (Chiba University, Japan) for providing us with a good protocol for whole mount in situ hybridization. We are also grateful to Drs. Yoshimitsu Kanai and Akihiro Harada, Ms. Chunjie Zhao, and Ms. Noriko Homma for their assistance in transgenic technology, and to Mrs. Haruyo Fukuda, Ms. Hiromi Sato, and Mr. Nobuhisa Ono-uchi for their technical and secretarial assistance.
Sen Takeda, Yoshiaki Yonekawa, Yosuke Tanaka, Yasushi Okada, Shigenori Nonaka, Nobutaka Hirokawa; Left-Right Asymmetry and Kinesin Superfamily Protein KIF3A: New Insights in Determination of Laterality and Mesoderm Induction by kif3A−/− Mice Analysis . J Cell Biol 17 May 1999; 145 (4): 825–836. doi: https://doi.org/10.1083/jcb.145.4.825
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