scholarly journals The Drosophila Neurogenin, Tap, controls axonal growth through the Wnt adaptor protein Dishevelled

2015 ◽  
Author(s):  
Liqun Yuan ◽  
Shu Hu ◽  
Zeynep Okray ◽  
Xi Ren ◽  
Natalie De Geest ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Cell Polarity ◽  
Mushroom Body ◽  
Planar Cell Polarity ◽  
Adaptor Protein ◽  
Axonal Growth ◽  
Neurite Growth ◽  
Fine Regulation ◽  
Early Neurogenesis

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.

scholarly journals Non-Canonical Wnt Signaling Regulates Cochlear Outgrowth and Planar Cell Polarity via Gsk3β Inhibition

2021 ◽  
Vol 9 ◽  
Author(s):  
Andre Landin Malt ◽  
Shaylyn Clancy ◽  
Diane Hwang ◽  
Alice Liu ◽  
Connor Smith ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Small Gtpase ◽  
Hair Bundle ◽  
Apical Surface ◽  
Canonical Wnt Signaling ◽  
Genetic Rescue ◽  
Genetic Ablation ◽  
Canonical Wnt

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.

scholarly journals Coupling of apical-basal polarity and planar cell polarity to interpret the Wnt signaling gradient in feather development

Development ◽  
2018 ◽  
Vol 145 (17) ◽  
pp. dev162792 ◽  
Author(s):  
Jianqiong Lin ◽  
Zhicao Yue
Keyword(s):  
Wnt Signaling ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Feather Development

scholarly journals The Wnt5/Planar Cell Polarity Pathway Regulates Axonal Development of the Drosophila Mushroom Body Neuron

2011 ◽  
Vol 31 (13) ◽  
pp. 4944-4954 ◽  
Author(s):  
K. Shimizu ◽  
M. Sato ◽  
T. Tabata
Keyword(s):  
Cell Polarity ◽  
Mushroom Body ◽  
Planar Cell Polarity ◽  
Planar Cell Polarity Pathway ◽  
Axonal Development

scholarly journals Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear

2019 ◽  
Vol 30 (18) ◽  
pp. 2422-2434 ◽  
Author(s):  
Cristy Tower-Gilchrist ◽  
Stephanie A. Zlatic ◽  
Dehong Yu ◽  
Qing Chang ◽  
Hao Wu ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Adaptor Protein ◽  
Rab Proteins ◽  
Convergent Extension ◽  
Cellular Polarity ◽  
Profound Hearing Loss ◽  
Recycling Endosomes ◽  
Axis Parallel ◽  
Rna Knockdown

Planar cell polarity (PCP) regulates coordinated cellular polarity among neighboring cells to establish a polarity axis parallel to the plane of the tissue. Disruption in PCP results in a range of developmental anomalies and diseases. A key feature of PCP is the polarized and asymmetric localization of several membrane PCP proteins, which is essential to establish the polarity axis to orient cells coordinately. However, the machinery that regulates the asymmetric partition of PCP proteins remains largely unknown. In the present study, we show Van gogh-like 2 (Vangl2) in early and recycling endosomes as made evident by colocalization with diverse endosomal Rab proteins. Vangl2 biochemically interacts with adaptor protein-3 complex (AP-3). Using short hairpin RNA knockdown, we found that Vangl2 subcellular localization was modified in AP-3–depleted cells. Moreover, Vangl2 membrane localization within the cochlea is greatly reduced in AP-3–deficient mocha mice, which exhibit profound hearing loss. In inner ears from AP-3–deficient mocha mice, we observed PCP-dependent phenotypes, such as misorientation and deformation of hair cell stereociliary bundles and disorganization of hair cells characteristic of defects in convergent extension that is driven by PCP. These findings demonstrate a novel role of AP-3–mediated sorting mechanisms in regulating PCP proteins.

scholarly journals Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways

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 ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Tubular Injury ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

TheXenopusreceptor tyrosine kinase Xror2 modulates morphogenetic movements of the axial mesoderm and neuroectoderm via Wnt signaling

Development ◽  
2002 ◽  
Vol 129 (22) ◽  
pp. 5227-5239 ◽  
Author(s):  
Hiroki Hikasa ◽  
Mikihito Shibata ◽  
Ichiro Hiratani ◽  
Masanori Taira
Keyword(s):  
Tyrosine Kinase ◽  
Wnt Signaling ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Dominant Negative ◽  
Treated Animal ◽  
Convergent Extension ◽  
Wild Type ◽  
Morphogenetic Movements ◽  
Planar Cell Polarity Pathway

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.

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