scholarly journals Draxin acts as a molecular rheostat of canonical Wnt signaling to control cranial neural crest EMT

2018 ◽  
Vol 217 (10) ◽  
pp. 3683-3697 ◽  
Author(s):  
Erica J. Hutchins ◽  
Marianne E. Bronner
Keyword(s):  
Wnt Signaling ◽  
Neural Crest ◽  
Neural Tube ◽  
Epithelial To Mesenchymal Transition ◽  
Cranial Neural Crest ◽  
Canonical Wnt Signaling ◽  
Mesenchymal Transition ◽  
Molecular Rheostat ◽  
Timing Of Initiation ◽  
Canonical Wnt

Neural crest cells undergo a spatiotemporally regulated epithelial-to-mesenchymal transition (EMT) that proceeds head to tailward to exit from the neural tube. In this study, we show that the secreted molecule Draxin is expressed in a transient rostrocaudal wave that mirrors this emigration pattern, initiating after neural crest specification and being down-regulated just before delamination. Functional experiments reveal that Draxin regulates the timing of cranial neural crest EMT by transiently inhibiting canonical Wnt signaling. Ectopic maintenance of Draxin in the cranial neural tube blocks full EMT; while cells delaminate, they fail to become mesenchymal and migratory. Loss of Draxin results in premature delamination but also in failure to mesenchymalize. These results suggest that a pulse of intermediate Wnt signaling triggers EMT and is necessary for its completion. Taken together, these data show that transient secreted Draxin mediates proper levels of canonical Wnt signaling required to regulate the precise timing of initiation and completion of cranial neural crest EMT.

scholarly journals Transcriptomic Identification of Draxin-Responsive Targets During Cranial Neural Crest EMT

2021 ◽  
Vol 12 ◽  
Author(s):  
Erica J. Hutchins ◽  
Michael L. Piacentino ◽  
Marianne E. Bronner
Keyword(s):  
Wnt Signaling ◽  
Neural Crest ◽  
Gene List ◽  
Hybridization Chain Reaction ◽  
Cranial Neural Crest ◽  
Canonical Wnt Signaling ◽  
Chain Reaction ◽  
Mesenchymal Transition ◽  
Neural Crest Development ◽  
Canonical Wnt

Canonical Wnt signaling plays an essential role in proper craniofacial morphogenesis, at least partially due to regulation of various aspects of cranial neural crest development. In an effort to gain insight into the etiology of craniofacial abnormalities resulting from Wnt signaling and/or cranial neural crest dysfunction, we sought to identify Wnt-responsive targets during chick cranial neural crest development. To this end, we leveraged overexpression of a canonical Wnt antagonist, Draxin, in conjunction with RNA-sequencing of cranial neural crest cells that have just activated their epithelial–mesenchymal transition (EMT) program. Through differential expression analysis, gene list functional annotation, hybridization chain reaction (HCR), and quantitative reverse transcription polymerase chain reaction (RT-qPCR), we validated a novel downstream target of canonical Wnt signaling in cranial neural crest – RHOB – and identified possible signaling pathway crosstalk underlying cranial neural crest migration. The results reveal novel putative targets of canonical Wnt signaling during cranial neural crest EMT and highlight important intersections across signaling pathways involved in craniofacial development.

scholarly journals Genetic interaction of Pax3 mutation and canonical Wnt signaling modulates neural tube defects and neural crest abnormalities

genesis ◽  
2021 ◽  
Author(s):  
Alexandra J. Palmer ◽  
Dawn Savery ◽  
Valentina Massa ◽  
Andrew J. Copp ◽  
Nicholas D. E. Greene
Keyword(s):  
Wnt Signaling ◽  
Neural Crest ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Genetic Interaction ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals A new transgenic reporter line reveals Wnt-dependent Snail2 reexpression and cranial neural crest differentiation in Xenopus

2019 ◽  
Author(s):  
Jiejing Li ◽  
Mark Perfetto ◽  
Christopher Materna ◽  
Rebecca Li ◽  
Hong Thi Tran ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Neural Crest ◽  
Fluorescent Protein ◽  
Developmental Stages ◽  
Egfp Expression ◽  
Cranial Neural Crest ◽  
Canonical Wnt Signaling ◽  
Reporter Line ◽  
Green Fluorescent ◽  
Canonical Wnt

AbstractDuring vertebrate embryogenesis, the cranial neural crest (CNC) forms at the neural plate border and subsequently migrates and differentiates into many types of cells. The transcription factor Snail2, which is induced by canonical Wnt signaling to be expressed in the early CNC, is pivotal for CNC induction and migration in Xenopus. However, snail2 expression is silenced during CNC migration, and its roles at later developmental stages remain unclear. We generated a transgenic X. tropicalis line that expresses enhanced green fluorescent protein (eGFP) driven by the snail2 promoter/enhancer, and observed eGFP expression not only in the pre-migratory and migrating CNC, but also the differentiating CNC. This transgenic line can be used directly to detect deficiencies in CNC development at various stages, including subtle perturbation of CNC differentiation. In situ hybridization and immunohistochemistry confirm that Snail2 is reexpressed in the differentiating CNC. Using a separate transgenic Wnt reporter line, we show that canonical Wnt signaling is also active in the differentiating CNC. Blocking Wnt signaling shortly after CNC migration causes reduced snail2 expression and impaired differentiation of CNC-derived head cartilage structures. These results suggest that Wnt signaling drives the reexpression of snail2 in the post-migratory CNC and regulates CNC differentiation.

scholarly journals Sox2 and canonical Wnt signaling interact to activate a developmental checkpoint coordinating morphogenesis with mesodermal fate acquisition

2020 ◽  
Author(s):  
Brian A. Kinney ◽  
Richard H. Row ◽  
Yu-Jung Tseng ◽  
Maxwell D. Weidmann ◽  
Holger Knaut ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cell Fate ◽  
Epithelial To Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Mesoderm Induction ◽  
Cell Fate Specification ◽  
Canonical Wnt Signaling ◽  
Mesodermal Cell ◽  
Mesenchymal Transition ◽  
Canonical Wnt

AbstractAnimal embryogenesis requires a precise coordination between morphogenesis and cell fate specification. It is unclear if there are mechanisms that prevent uncoupling of these processes to ensure robust development. During mesoderm induction, mesodermal fate acquisition is tightly coordinated with the morphogenetic process of epithelial to mesenchymal transition (EMT). In zebrafish, cells exist transiently in a partial EMT state during mesoderm induction. Here we show that cells expressing the neural inducing transcription factor Sox2 are held in the partial EMT state, stopping them from completing the EMT and joining the mesodermal territory. This is critical for preventing ectopic neural tissue from forming. The mechanism involves specific interactions between Sox2 and the mesoderm inducing canonical Wnt signaling pathway. When Wnt signaling is inhibited in Sox2 expressing cells trapped in the partial EMT, cells are now able to exit into the mesodermal territory, but form an ectopic spinal cord instead of mesoderm. Our work identifies a critical developmental checkpoint that ensures that morphogenetic movements establishing the mesodermal germ layer are accompanied by robust mesodermal cell fate acquisition.

scholarly journals Cadherin-6B proteolysis promotes the neural crest cell epithelial-to-mesenchymal transition through transcriptional regulation

2016 ◽  
Vol 215 (5) ◽  
pp. 735-747 ◽  
Author(s):  
Andrew T. Schiffmacher ◽  
Vivien Xie ◽  
Lisa A. Taneyhill
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cell ◽  
Cranial Neural Crest ◽  
Mesenchymal Transition ◽  
Effector Genes ◽  
A Disintegrin And Metalloproteinase ◽  
And Migration ◽  
Cranial Neural Crest Cells

During epithelial-to-mesenchymal transitions (EMTs), cells disassemble cadherin-based junctions to segregate from the epithelia. Chick premigratory cranial neural crest cells reduce Cadherin-6B (Cad6B) levels through several mechanisms, including proteolysis, to permit their EMT and migration. Serial processing of Cad6B by a disintegrin and metalloproteinase (ADAM) proteins and γ-secretase generates intracellular C-terminal fragments (CTF2s) that could acquire additional functions. Here we report that Cad6B CTF2 possesses a novel pro-EMT role by up-regulating EMT effector genes in vivo. After proteolysis, CTF2 remains associated with β-catenin, which stabilizes and redistributes both proteins to the cytosol and nucleus, leading to up-regulation of β-catenin, CyclinD1, Snail2, and Snail2 promoter-based GFP expression in vivo. A CTF2 β-catenin–binding mutant, however, fails to alter gene expression, indicating that CTF2 modulates β-catenin–responsive EMT effector genes. Notably, CTF2 association with the endogenous Snail2 promoter in the neural crest is β-catenin dependent. Collectively, our data reveal how Cad6B proteolysis orchestrates multiple pro-EMT regulatory inputs, including CTF2-mediated up-regulation of the Cad6B repressor Snail2, to ensure proper cranial neural crest EMT.

scholarly journals Enhanced Activation of Canonical Wnt Signaling Confers Mesoderm-Derived Parietal Bone with Similar Osteogenic and Skeletal Healing Capacity to Neural Crest-Derived Frontal Bone

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0138059 ◽  
Author(s):  
Shuli Li ◽  
Natalina Quarto ◽  
Kshemendra Senarath-Yapa ◽  
Nathaniel Grey ◽  
Xue Bai ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Neural Crest ◽  
Parietal Bone ◽  
Frontal Bone ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt
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