Although microtubule-dependent motors are known to play many essential functions in eukaryotic cells, their role in the context of the developing vertebrate embryo is less well understood. Here we show that the zebrafish ale oko (ako) locus encodes the p50 component of the dynactin complex. Loss of ako function results in a degeneration of photoreceptors and mechanosensory hair cells. Additionally, mutant Müller cells lose apical processes and their perikarya translocate rapidly towards the vitreal surface of the retina. This is accompanied by the accumulation of the apical determinants Nok and Has/aPKC in their cell bodies. ako is required cell-autonomously for the maintenance of the apical process but not for cell body positioning in Müller glia. At later stages, the retinotectal projection also degenerates in ako mutants. These results indicate that the p50 component of the dynactin complex is essential for the survival of sensory neurons and the maintenance of ganglion cell axons, and functions as a major determinant of apicobasal polarity in retinal radial glia.
Drs Jon Clarke, Ching-Hwa Sun and Paula Alexandre provided helpful comments on previous versions of this manuscript. We are also grateful to Drs Jeffery Corwin, Herbert Steinbeisser, Herwig Baier and Pamala Raymond for antibodies and transgenic animals. Drs Rachel Wong and Chi-Bin Chien provided helpful advice regarding live imaging of zebrafish embryos. The ako locus was initially mapped by the mapping facility at the University of Louisville. These studies were supported by a grant from the Knights Templar Eye Foundation (to X.J.) and an NIH R01 EY016859 award (to J.M.). Deposited in PMC for release after 12 months.
