Faculty Collaboration Database

Loss of Llgl1 in retinal neuroepithelia reveals links between apical domain size, Notch activity and neurogenesis. Development 2012 May;139(9):1599-610

Date

04/12/2012

Pubmed ID

22492354

Pubmed Central ID

PMC3317966

DOI

10.1242/dev.078097

Scopus ID

2-s2.0-84859297815 (requires institutional sign-in at Scopus site)   62 Citations

Abstract

To gain insights into the cellular mechanisms of neurogenesis, we analyzed retinal neuroepithelia deficient for Llgl1, a protein implicated in apicobasal cell polarity, asymmetric cell division, cell shape and cell cycle exit. We found that vertebrate retinal neuroepithelia deficient for Llgl1 retained overt apicobasal polarity, but had expanded apical domains. Llgl1 retinal progenitors also had increased Notch activity and reduced rates of neurogenesis. Blocking Notch function by depleting Rbpj restored normal neurogenesis. Experimental expansion of the apical domain, through inhibition of Shroom3, also increased Notch activity and reduced neurogenesis. Significantly, in wild-type retina, neurogenic retinal progenitors had smaller apical domains compared with proliferative neuroepithelia. As nuclear position during interkinetic nuclear migration (IKNM) has been previously linked with cell cycle exit, we analyzed this phenomenon in cells depleted of Llgl1. We found that although IKNM was normal, the relationship between nuclear position and neurogenesis was shifted away from the apical surface, consistent with increased pro-proliferative and/or anti-neurogenic signals associated with the apical domain. These data, in conjunction with other findings, suggest that, in retinal neuroepithelia, the size of the apical domain modulates the strength of polarized signals that influence neurogenesis.

Author List

Clark BS, Cui S, Miesfeld JB, Klezovitch O, Vasioukhin V, Link BA

Authors

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

MESH terms used to index this publication - Major topics in bold

Animals
Bromodeoxyuridine
Cell Cycle Proteins
Microfilament Proteins
Neuroepithelial Cells
Neurogenesis
Oligonucleotides
Receptors, Notch
Retina
Time-Lapse Imaging
Zebrafish
Zebrafish Proteins