RT Journal Article SR Electronic T1 KLC4 shapes axon arbors during development and mediates adult behavior JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.09.26.461872 DO 10.1101/2021.09.26.461872 A1 Haynes, Elizabeth M. A1 Burnett, Korri H. A1 He, Jiaye A1 Jean-Pierre, Marcel A1 Jarzyna, Martin A1 Eliceiri, Kevin W. A1 Huisken, Jan A1 Halloran, Mary C. YR 2022 UL http://biorxiv.org/content/early/2022/09/06/2021.09.26.461872.abstract AB Development of elaborate and polarized neuronal morphology requires precisely regulated transport of cellular cargos by motor proteins such as kinesin-1. Kinesin-1 has numerous cellular cargos which must be delivered to unique neuronal compartments. The process by which this motor selectively transports and delivers cargo to regulate neuronal morphogenesis is poorly understood, although the cargo-binding kinesin light chain (KLC) subunits contribute to specificity. Our work implicates one such subunit, KLC4, as an essential regulator of axon branching and arborization pattern of sensory neurons during development. Using live imaging approaches in klc4 mutant zebrafish, we show that KLC4 is required for stabilization of nascent axon branches, proper microtubule (MT) dynamics, and endosomal transport. Furthermore, KLC4 is required for proper tiling of peripheral axon arbors: in klc4 mutants, peripheral axons showed abnormal fasciculation, a behavior characteristic of central axons. This result suggests that KLC4 patterns axonal compartments and helps establish molecular differences between central and peripheral axons. Finally, we find that klc4 mutant larva are hypersensitive to touch and adults show anxiety-like behavior in a novel tank test, implicating klc4 as a new gene involved in stress response circuits.Competing Interest StatementK. Eliceiri is a consultant for Bruker, the manufacturer of the Opterra Swept Field Confocal microscope used in this work.