@article{e85742ba9afc41968f7e8bb56459fa29,
title = "Dynamic Polarization of Rab11a Modulates Crb2a Localization and Impacts Signaling to Regulate Retinal Neurogenesis",
abstract = "Interkinetic nuclear migration (IKNM) is the process in which pseudostratified epithelial nuclei oscillate from the apical to basal surface and in phase with the mitotic cycle. In the zebrafish retina, neuroepithelial retinal progenitor cells (RPCs) increase Notch activity with apical movement of the nuclei, and the depth of nuclear migration correlates with the probability that the next cell division will be neurogenic. This study focuses on the mechanisms underlying the relationships between IKNM, cell signaling, and neurogenesis. In particular, we have explored the role IKNM has on endosome biology within RPCs. Through genetic manipulation and live imaging in zebrafish, we find that early (Rab5-positive) and recycling (Rab11a-positive) endosomes polarize in a dynamic fashion within RPCs and with reference to nuclear position. Functional analyses suggest that dynamic polarization of recycling endosomes and their activity within the neuroepithelia modulates the subcellular localization of Crb2a, consequently affecting multiple signaling pathways that impact neurogenesis including Notch, Hippo, and Wnt activities. As nuclear migration is heterogenous and asynchronous among RPCs, Rab11a-affected signaling within the neuroepithelia is modulated in a differential manner, providing mechanistic insight to the correlation of IKNM and selection of RPCs to undergo neurogenesis.",
keywords = "Rab11, crumbs, endocytosis, interkinetic nuclear migration, neurogenesis, recycling endosome",
author = "Clark, {Brian S.} and Miesfeld, {Joel B.} and Flinn, {Michael A.} and Collery, {Ross F.} and Link, {Brian A.}",
note = "Funding Information: All RNAseq experiments were performed in VANTAGE (Vanderbilt University, Nashville, TN, USA). Vantage was supported by the Vanderbilt Ingram Cancer Center (P30 CA68485), the Vanderbilt Vision Center (P30 EY08126), and the NIH/NCRR (G20 RR030956). The authors also wish to thank Michael Cliff, William Hudzinski, and Brandon Mikulski for their assistance with zebrafish husbandry and Clive Wells for TEM assistance. We also thank Abbie Jensen (UMASS Amherst) for sharing reagents used in this study to generate Crb2a plasmids. Funding. This project was supported by the National Institutes of Health (T32 EY014536 to BC, JM, and MF, R00EY027844 to BC, K99EY030944 to JM, T32 HL134643 to MF, F32 HL150958 to MF, R01 EY014167 to BL, and P30 EY001931 and C06RR016511 to the Medical College of Wisconsin, Department of Ophthalmology and Vision Sciences), the Medical College of Wisconsin Cardiovascular Center's A.O. Smith Fellowship Scholars Program to MF, the E. Matilda Ziegler Foundation for the Blind grant to RC, as well as by an unrestricted grant to the John F. Hardesty, MD Department of Ophthalmology and Visual Sciences at Washington University from Research to Prevent Blindness supporting BC. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Clark, Miesfeld, Flinn, Collery and Link.",
year = "2021",
month = feb,
day = "9",
doi = "10.3389/fcell.2020.608112",
language = "English",
volume = "8",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
}