Swap70b acts downstream of Wnt11 signalling to regulate zebrafish convergence and extension cell movements

During vertebrate gastrulation, convergence and extension (CE) cell movements narrow the body axis medial-laterally (convergence) and extend it anterior-posteriorly (extension). In zebrafish, Wnt11 (silberblick) and Wnt5b (pipetail) mutants exhibited widening and shortening of the body axes characte...

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Main Author: Xu, Xiaoou
Format: Thesis (University of Nottingham only)
Language:English
Published: 2015
Online Access:https://eprints.nottingham.ac.uk/28604/
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author Xu, Xiaoou
author_facet Xu, Xiaoou
author_sort Xu, Xiaoou
building Nottingham Research Data Repository
collection Online Access
description During vertebrate gastrulation, convergence and extension (CE) cell movements narrow the body axis medial-laterally (convergence) and extend it anterior-posteriorly (extension). In zebrafish, Wnt11 (silberblick) and Wnt5b (pipetail) mutants exhibited widening and shortening of the body axes characteristic for CE cell movements defects during gastrulation. It was subsequently reported that Wnt signalling resulted in activation of Rho GTPases and rearrangements of the F-actin cytoskeleton, establishing that CE cell movements are regulated through the non canonical Wnt/PCP pathway. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and it was recently found that Def6a, a GEF for Rac1, Cdc42, and RhoA, was the downstream target of Wnt5b signalling. In this thesis, morpholino-mediated knockdown of gene expression in conjunction with phenotypic rescue experiments revealed that Swap70b, a GEF protein closely related to Def6a, functions downstream of Wnt11. Swap70b morphants exhibited broader and shorter body axis with no apparent defect in cell fate specification, and ectopic Swap70b expression robustly rescued wnt11 morphants, establishing Swap70b as a novel member of the non-canonical Wnt/PCP pathway downstream of Wnt11. The following phenotypic rescue experiments demonstrated that Swap70b and Def6a execute both distinct and overlapping functions in the modulation of CE cell movements. In addition, as previously shown for Wnt11 (silberblick) and Wnt5b (pipetail) double mutants, Swap70b and Def6a double mutant morphants exhibited a more severe CE cell movement defect, suggesting that Swap70b and Def6a delineate Wnt11 and Wnt5b signalling pathways.
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spelling nottingham-286042025-02-28T11:34:04Z https://eprints.nottingham.ac.uk/28604/ Swap70b acts downstream of Wnt11 signalling to regulate zebrafish convergence and extension cell movements Xu, Xiaoou During vertebrate gastrulation, convergence and extension (CE) cell movements narrow the body axis medial-laterally (convergence) and extend it anterior-posteriorly (extension). In zebrafish, Wnt11 (silberblick) and Wnt5b (pipetail) mutants exhibited widening and shortening of the body axes characteristic for CE cell movements defects during gastrulation. It was subsequently reported that Wnt signalling resulted in activation of Rho GTPases and rearrangements of the F-actin cytoskeleton, establishing that CE cell movements are regulated through the non canonical Wnt/PCP pathway. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and it was recently found that Def6a, a GEF for Rac1, Cdc42, and RhoA, was the downstream target of Wnt5b signalling. In this thesis, morpholino-mediated knockdown of gene expression in conjunction with phenotypic rescue experiments revealed that Swap70b, a GEF protein closely related to Def6a, functions downstream of Wnt11. Swap70b morphants exhibited broader and shorter body axis with no apparent defect in cell fate specification, and ectopic Swap70b expression robustly rescued wnt11 morphants, establishing Swap70b as a novel member of the non-canonical Wnt/PCP pathway downstream of Wnt11. The following phenotypic rescue experiments demonstrated that Swap70b and Def6a execute both distinct and overlapping functions in the modulation of CE cell movements. In addition, as previously shown for Wnt11 (silberblick) and Wnt5b (pipetail) double mutants, Swap70b and Def6a double mutant morphants exhibited a more severe CE cell movement defect, suggesting that Swap70b and Def6a delineate Wnt11 and Wnt5b signalling pathways. 2015-03-15 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/28604/2/PhD%20thesis%20-Xiaoou%20Xu%20%284121526%29.pdf Xu, Xiaoou (2015) Swap70b acts downstream of Wnt11 signalling to regulate zebrafish convergence and extension cell movements. PhD thesis, University of Nottingham.
spellingShingle Xu, Xiaoou
Swap70b acts downstream of Wnt11 signalling to regulate zebrafish convergence and extension cell movements
title Swap70b acts downstream of Wnt11 signalling to regulate zebrafish convergence and extension cell movements
title_full Swap70b acts downstream of Wnt11 signalling to regulate zebrafish convergence and extension cell movements
title_fullStr Swap70b acts downstream of Wnt11 signalling to regulate zebrafish convergence and extension cell movements
title_full_unstemmed Swap70b acts downstream of Wnt11 signalling to regulate zebrafish convergence and extension cell movements
title_short Swap70b acts downstream of Wnt11 signalling to regulate zebrafish convergence and extension cell movements
title_sort swap70b acts downstream of wnt11 signalling to regulate zebrafish convergence and extension cell movements
url https://eprints.nottingham.ac.uk/28604/