J. Cell Biol., Volume 145, Number 4, May 17, 1999 825-836

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 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.

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