Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0010125
Title: A vertebrate-specific Chp-PAK-PIX pathway maintains E-cadherin at adherens junctions during zebrafish epiboly
Authors: Tay H.G. 
Ng Y.W.
Manser E. 
Keywords: adaptor PAK interacting exchange factor
adaptor protein
beta catenin
F actin
messenger RNA
oligonucleotide
p21 activated kinase
phosphotransferase
protein
Rho guanine nucleotide binding protein
unclassified drug
uvomorulin
cadherin
guanine nucleotide exchange factor
rho guanine nucleotide exchange factors
animal tissue
article
blood brain barrier
cell adhesion
cell junction
cell motion
cell vacuole
controlled study
embryo
enzyme activation
gastrulation
mutant
nonhuman
nucleotide sequence
protein assembly
protein depletion
protein localization
signal transduction
vertebrate
zebra fish
animal
animal embryo
metabolism
physiology
signal transduction
Danio rerio
Vertebrata
Adherens Junctions
Animals
Cadherins
Cell Adhesion
Cell Movement
Embryo, Nonmammalian
Guanine Nucleotide Exchange Factors
p21-Activated Kinases
rho GTP-Binding Proteins
Signal Transduction
Vertebrates
Zebrafish
Issue Date: 2010
Citation: Tay H.G., Ng Y.W., Manser E. (2010). A vertebrate-specific Chp-PAK-PIX pathway maintains E-cadherin at adherens junctions during zebrafish epiboly. PLoS ONE 5 (4) : e10125. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0010125
Rights: Attribution 4.0 International
Abstract: Background: In early vertebrate development, embryonic tissues modulate cell adhesiveness and acto-myosin contractility to correctly orchestrate the complex processes of gastrulation. E-cadherin (E-cadh) is the earliest expressed cadherin and is needed in the mesendodermal progenitors for efficient migration [1,2]. Regulatory mechanisms involving directed E-cadh trafficking have been invoked downstream of Wnt11/5 signaling [3]. This non-canonical Wnt pathway regulates RhoA-ROK/ DAAM1 to control the acto-myosin network. However, in this context nothing is known of the intracellular signals that participate in the correct localization of E-cadh, other than a need for Rab5c signaling [3]. Methodology/Principal Findings: By studying loss of Chp induced by morpholino-oligonucleotide injection in zebrafish, we find that the vertebrate atypical Rho-GTPase Chp is essential for the proper disposition of cells in the early embryo. The underlying defect is not leading edge F-actin assembly (prominent in the cells of the envelope layer), but rather the failure to localize E-cadh and ?-catenin at the adherens junctions. Loss of Chp results in delayed epiboly that can be rescued by mRNA co-injection, and phenocopies zebrafish E-cadh mutants [4,5]. This new signaling pathway involves activation of an effector kinase PAK, and involvement of the adaptor PAK-interacting exchange factor PIX. Loss of signaling by any of the three components results in similar underlying defects, which is most prominent in the epithelial-like envelope layer. Conclusions/Significance: Our current study uncovers a developmental pathway involving Chp/PAK/PIX signaling, which helps co-ordinate E-cadh disposition to promote proper cell adhesiveness, and coordinate movements of the three major cell layers in epiboly. Our data shows that without Chp signaling, E-cadh shifts to intracellular vesicles rather than the adhesive contacts needed for directed cell movement. These events may mirror the requirement for PAK2 signaling essential for the proper formation of the blood-brain barrier [6,7].© 2010 Tay et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161811
ISSN: 19326203
DOI: 10.1371/journal.pone.0010125
Rights: Attribution 4.0 International
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