Left-Right Asymmetry and Kinesin Superfamily Protein KIF3A: New Insights in Determination of Laterality and Mesoderm Induction by kif3A-/- Mice Analysis

doi:10.1083/jcb.145.4.825

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© The Rockefeller University Press, 0021-9525/1999//825 $5.00
The Journal of Cell Biology, Volume 145, Number 4, , 1999 825-836

Regular Articles

Left-Right Asymmetry and Kinesin Superfamily Protein KIF3A: New Insights in Determination of Laterality and Mesoderm Induction by kif3A^–^/– Mice Analysis

Sen Takeda, Yoshiaki Yonekawa, Yosuke Tanaka, Yasushi Okada, Shigenori Nonaka, and 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

KIF3A is a classical member of the kinesin superfamily proteins(KIFs), ubiquitously expressed although predominantly in neuraltissues, and which forms a heterotrimeric KIF3 complex withKIF3B or KIF3C and an associated protein, KAP3. To elucidate the function of the kif3A gene in vivo, we made kif3A knockoutmice. kif3A^–/– embryos displayed severe developmentalabnormalities characterized by neural tube degeneration andmesodermal and caudal dysgenesis and died during the midgestationalperiod at $~$ 10.5 dpc (days post coitum), possibly resulting fromcardiovascular insufficiency. Whole mount in situ hybridizationof Pax6 revealed a normal pattern while staining by sonic hedgehog(shh) and Brachyury (T) exhibited abnormal patterns in theanterior-posterior (A-P) direction at both mesencephalic andthoracic levels. These results suggest that KIF3A might beinvolved in mesodermal patterning and in turn neurogenesis.

Key Words: microtubule • kinesin • kif3A • gene targeting • left-right asymmetry

Abbreviations used in this paper: AP, alkaline phosphatase; dpc, days post coitum; ES, embryonic stem; IFT, intraciliary-flagellar transport; KIF, kinesin superfamily protein; MT, microtubule; RT, room temperature; VEC-DIC/FL, simultaneous observation of video-enhanced contrast DIC and fluorescent images.

We should like to express our gratitude to Dr. Toshimichi Yoshida(Mie University, Japan) for the anti-axonemal outer arm dyneinantibody (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 andshh probe; Drs. Yumiko Saga (National Institute of Health Science,Japan) and Bernhard G. Herrmann (Max-Planck Institut fürEntwicklungsbiologie, Tübingen, Germany) for the Brachyuryprobe; Dr. Peter Gruss (Max-Planck Institut für BiophysikalischeChemie, Göttingen, Germany) for the Pax6 probe. We appreciateDr. Mika Karasawa (Chiba University, Japan) for providing uswith 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 assistancein transgenic technology, and to Mrs. Haruyo Fukuda, Ms. HiromiSato, and Mr. Nobuhisa Ono-uchi for their technical and secretarialassistance.

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