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The unconventional kinesin Kif26a is required for the guidance of major axon tracts in the developing mouse brain

Srisathya SrinivasaniD, Kayla Louie, Timothy Casey-Clyde, Zixin Wei, Morgan Krueger, Edith P. KarunaiD, Ryuichi NishinakamuraiD, Konstantinos S. ZarbalisiD, Qizhi GongiD, Sergi SimóiD, Hsin‐Yi Henry HoiD

Abstract

Kif26a and Kif26b encode a family of unconventional kinesins with emerging roles in neurodevelopment, and mutations in both genes have been implicated in a spectrum of neurodevelopmental disorders. The precise mechanisms by which the Kif26 family orchestrates mammalian brain development, however, remain unclear. In this study, we show that Kif26a and Kif26b are expressed in distinct regions of the developing mouse brain. Using a new allelic series in mice, we demonstrate that Kif26a is required for the guidance of multiple forebrain axon tracts. This requirement is direct and cell autonomous, as cell proliferation, survival, and cortical layering are unaffected in the Kif26a mutants. These guidance defects closely resemble those reported for the Fzd3-Celsr3-Dystroglycan pathway, suggesting that Kif26a may participate within this conserved signaling axis to steer growing axons.

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