@article{eb407ac6dfff4ef0a4daa739ede7e19a,
title = "Repeated nuclear translocations underlie photoreceptor positioning and lamination of the outer nuclear layer in the mammalian retina",
abstract = "In development, almost all stratified neurons must migrate from their birthplace to the appropriate neural layer. Photoreceptors reside in the most apical layer of the retina, near their place of birth. Whether photoreceptors require migratory events for fine-positioning and/or retention within this layer is not well understood. Here, we show that photoreceptor nuclei of the developing mouse retina cyclically exhibit rapid, dynein-1-dependent translocation toward the apical surface, before moving more slowly in the basal direction, likely due to passive displacement by neighboring retinal nuclei. Attenuating dynein 1 function in rod photoreceptors results in their ectopic basal displacement into the outer plexiform layer and inner nuclear layer. Synapse formation is also compromised in these displaced cells. We propose that repeated, apically directed nuclear translocation events are necessary to ensure retention of post-mitotic photoreceptors within the emerging outer nuclear layer during retinogenesis, which is critical for correct neuronal lamination.",
keywords = "development, dynein, interkinetic nuclear migration, lamination, motor proteins, neuronal migration, retina, synaptogenesis, tissue differentiation, translocation",
author = "Aghaizu, {Nozie D.} and Warre-Cornish, {Katherine M.} and Robinson, {Martha R.} and Waldron, {Paul V.} and Maswood, {Ryea N.} and Smith, {Alexander J.} and Ali, {Robin R.} and Pearson, {Rachael A.}",
note = "Funding Information: We thank Prof. M. Carandini for assistance with data analysis, O. Semenyuk at the IoO vector production facility for technical support, L. Abelleira-Hervas and J. Hoke for animal husbandry, and the UCL Cell and Developmental Biology Imaging Unit for imaging assistance. We thank A. Kalargyrou for help with maintaining explants and Nrl.Cre+/? lines and M. Rizzi for constructive criticism of earlier drafts of the manuscript. The graphical abstract was created using BioRender. This work was supported by the Royal Society (UF120046 and RG080398), Moorfields Eye Charity (ST1209J, E170004A, R150032A, and R180005A), Fight for Sight (1448/1449), RP Fighting Blindness, Medical Research Council UK (mr/j004553/1), and Wellcome Trust (082217). N.D.A. was a UCL Grand Challenge PhD student and Fight for Sight-funded post-doctoral research associate. K.M.W.-C. P.V.W. and M.R.R. were Wellcome Trust/MRC PhD students. Conceptualization, N.D.A. K.M.W.-C. and R.A.P.; methodology, N.D.A. K.M.W.-C. and R.A.P.; software, N.D.A. and M.R.R.; validation, N.D.A. and K.M.W.-C.; formal analysis, N.D.A. M.R.R. and P.V.W.; investigation, N.D.A. K.M.W.-C. and P.V.W.; resources, R.R.A. and R.A.P.; writing ? original draft, N.D.A. and R.A.P.; writing ? review & editing, N.D.A. A.J.S. R.R.A. and R.A.P.; funding acquisition, R.R.A. and R.A.P.; supervision, R.A.P. The authors declare no competing interests Funding Information: This work was supported by the Royal Society ( UF120046 and RG080398 ), Moorfields Eye Charity ( ST1209J , E170004A , R150032A , and R180005A ), Fight for Sight ( 1448/1449 ), RP Fighting Blindness , Medical Research Council UK ( mr/j004553/1 ), and Wellcome Trust ( 082217) . N.D.A. was a UCL Grand Challenge PhD student and Fight for Sight-funded post-doctoral research associate. K.M.W.-C., P.V.W., and M.R.R. were Wellcome Trust/MRC PhD students. Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = aug,
day = "3",
doi = "10.1016/j.celrep.2021.109461",
language = "English",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier BV",
number = "5",
}