Dynamic Polarization of Rab11a Modulates Crb2a Localization and Impacts Signaling to Regulate Retinal Neurogenesis. Front Cell Dev Biol 2020;8:608112
Date
02/27/2021Pubmed ID
33634099Pubmed Central ID
PMC7900515DOI
10.3389/fcell.2020.608112Scopus ID
2-s2.0-85101223534 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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.
Author List
Clark BS, Miesfeld JB, Flinn MA, Collery RF, Link BAAuthors
Ross F. Collery PhD Assistant Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMichael Andrew Flinn Postdoctoral Fellow in the Physiology department at Medical College of Wisconsin
Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Joel Bryan Miesfeld PhD Assistant Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
