scholarly journals Wnt-signaling and planar cell polarity genes regulate axon guidance along the anteroposterior axis inC. elegans

2013 ◽  
Vol 74 (8) ◽  
pp. 781-796 ◽  
Author(s):  
Brian D. Ackley

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.





2015 ◽  
Author(s):  
Liqun Yuan ◽  
Shu Hu ◽  
Zeynep Okray ◽  
Xi Ren ◽  
Natalie De Geest ◽  
...  

AbstractThe Neurogenin (Ngn) transcription factors control early neurogenesis and neurite outgrowth in mammalian cortex. In contrast to their proneural activity, their function in neurite growth is poorly understood. Drosophila has a single predicted Ngn homologue called Tap, whose function is completely unknown. Here we show that Tap is not a proneural protein in Drosophila but is required for proper axonal growth and guidance of neurons of the mushroom body (MB), a neuropile required for associative learning and memory. Genetic and expression analyses suggest that Tap inhibits excessive axonal growth by fine regulation of the levels of the Wnt signaling adaptor protein, Dishevelled.SummaryThe Drosophila Neurogenin homologue, Target of Pox neuro (Tap), prevents axonal overgrowth by regulating the Wnt Planar Cell Polarity pathway adaptor protein Dishevelled.





2009 ◽  
Vol 18 (14) ◽  
pp. 2532-2542 ◽  
Author(s):  
H. Happe ◽  
W. N. Leonhard ◽  
A. van der Wal ◽  
B. van de Water ◽  
I. S. Lantinga-van Leeuwen ◽  
...  


Development ◽  
2002 ◽  
Vol 129 (22) ◽  
pp. 5227-5239 ◽  
Author(s):  
Hiroki Hikasa ◽  
Mikihito Shibata ◽  
Ichiro Hiratani ◽  
Masanori Taira

The Spemann organizer plays a central role in neural induction, patterning of the neuroectoderm and mesoderm, and morphogenetic movements during early embryogenesis. By seeking genes whose expression is activated by the organizer-specific LIM homeobox gene Xlim-1 in Xenopusanimal caps, we isolated the receptor tyrosine kinase Xror2. Xror2 is expressed initially in the dorsal marginal zone, then in the notochord and the neuroectoderm posterior to the midbrain-hindbrain boundary. mRNA injection experiments revealed that overexpression of Xror2 inhibits convergent extension of the dorsal mesoderm and neuroectoderm in whole embryos, as well as the elongation of animal caps treated with activin, whereas it does not appear to affect cell differentiation of neural tissue and notochord. Interestingly, mutant constructs in which the kinase domain was point-mutated or deleted (named Xror2-TM) also inhibited convergent extension, and did not counteract the wild-type, suggesting that the ectodomain of Xror2 per se has activities that may be modulated by the intracellular domain. In relation to Wnt signaling for planar cell polarity, we observed: (1) the Frizzled-like domain in the ectodomain is required for the activity of wild-type Xror2 and Xror2-TM; (2) co-expression of Xror2 with Xwnt11, Xfz7, or both,synergistically inhibits convergent extension in embryos; (3) inhibition of elongation by Xror2 in activin-treated animal caps is reversed by co-expression of a dominant negative form of Cdc42 that has been suggested to mediate the planar cell polarity pathway of Wnt; and (4) the ectodomain of Xror2 interacts with Xwnts in co-immunoprecipitation experiments. These results suggest that Xror2 cooperates with Wnts to regulate convergent extension of the axial mesoderm and neuroectoderm by modulating the planar cell polarity pathway of Wnt.



2011 ◽  
Vol 20 (2) ◽  
pp. 163-176 ◽  
Author(s):  
Bo Gao ◽  
Hai Song ◽  
Kevin Bishop ◽  
Gene Elliot ◽  
Lisa Garrett ◽  
...  


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