Zebrafish models of non-canonical Wnt/planar cell polarity signalling: fishing for valuable insight into vertebrate polarized cell behavior

2017 ◽  
Vol 6 (3) ◽  
pp. e267 ◽  
Author(s):  
Maria Jussila ◽  
Brian Ciruna
Author(s):  
Andre Landin Malt ◽  
Shaylyn Clancy ◽  
Diane Hwang ◽  
Alice Liu ◽  
Connor Smith ◽  
...  

During development, sensory hair cells (HCs) in the cochlea assemble a stereociliary hair bundle on their apical surface with planar polarized structure and orientation. We have recently identified a non-canonical, Wnt/G-protein/PI3K signaling pathway that promotes cochlear outgrowth and coordinates planar polarization of the HC apical cytoskeleton and alignment of HC orientation across the cochlear epithelium. Here, we determined the involvement of the kinase Gsk3β and the small GTPase Rac1 in non-canonical Wnt signaling and its regulation of the planar cell polarity (PCP) pathway in the cochlea. We provided the first in vivo evidence for Wnt regulation of Gsk3β activity via inhibitory Ser9 phosphorylation. Furthermore, we carried out genetic rescue experiments of cochlear defects caused by blocking Wnt secretion. We showed that cochlear outgrowth was partially rescued by genetic ablation of Gsk3β but not by expression of stabilized β-catenin; while PCP defects, including hair bundle polarity and junctional localization of the core PCP proteins Fzd6 and Dvl2, were partially rescued by either Gsk3β ablation or constitutive activation of Rac1. Our results identify Gsk3β and likely Rac1 as downstream components of non-canonical Wnt signaling and mediators of cochlear outgrowth, HC planar polarity, and localization of a subset of core PCP proteins in the cochlea.


2014 ◽  
Vol 328 (2) ◽  
pp. 284-295 ◽  
Author(s):  
Michael Sebbagh ◽  
Jean-Paul Borg

GigaScience ◽  
2020 ◽  
Vol 9 (11) ◽  
Author(s):  
Paria Pooyan ◽  
Razieh Karamzadeh ◽  
Mehdi Mirzaei ◽  
Anna Meyfour ◽  
Ardeshir Amirkhan ◽  
...  

Abstract Background Generation of oligodendrocytes is a sophisticated multistep process, the mechanistic underpinnings of which are not fully understood and demand further investigation. To systematically profile proteome dynamics during human embryonic stem cell differentiation into oligodendrocytes, we applied in-depth quantitative proteomics at different developmental stages and monitored changes in protein abundance using a multiplexed tandem mass tag-based proteomics approach. Findings Our proteome data provided a comprehensive protein expression profile that highlighted specific expression clusters based on the protein abundances over the course of human oligodendrocyte lineage differentiation. We identified the eminence of the planar cell polarity signalling and autophagy (particularly macroautophagy) in the progression of oligodendrocyte lineage differentiation—the cooperation of which is assisted by 106 and 77 proteins, respectively, that showed significant expression changes in this differentiation process. Furthermore, differentially expressed protein analysis of the proteome profile of oligodendrocyte lineage cells revealed 378 proteins that were specifically upregulated only in 1 differentiation stage. In addition, comparative pairwise analysis of differentiation stages demonstrated that abundances of 352 proteins differentially changed between consecutive differentiation time points. Conclusions Our study provides a comprehensive systematic proteomics profile of oligodendrocyte lineage cells that can serve as a resource for identifying novel biomarkers from these cells and for indicating numerous proteins that may contribute to regulating the development of myelinating oligodendrocytes and other cells of oligodendrocyte lineage. We showed the importance of planar cell polarity signalling in oligodendrocyte lineage differentiation and revealed the autophagy-related proteins that participate in oligodendrocyte lineage differentiation.


Development ◽  
2010 ◽  
Vol 137 (20) ◽  
pp. 3459-3468 ◽  
Author(s):  
P. Oteiza ◽  
M. Koppen ◽  
M. Krieg ◽  
E. Pulgar ◽  
C. Farias ◽  
...  

2009 ◽  
Vol 126 ◽  
pp. S132
Author(s):  
Masatake Kai ◽  
Nina Buchan ◽  
Carl-Philipp Heisenberg ◽  
Masazumi Tada

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