scholarly journals Cadherin 6 promotes neural crest cell detachment via F-actin regulation and influences active Rho distribution during epithelial-to-mesenchymal transition

Development ◽  
2014 ◽  
Vol 141 (12) ◽  
pp. 2506-2515 ◽  
Author(s):  
M. R. Clay ◽  
M. C. Halloran
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cell ◽  
Cell Detachment ◽  
Mesenchymal Transition ◽  
Crest Cell

scholarly journals Cadherin-6B is proteolytically processed during epithelial-to-mesenchymal transitions of the cranial neural crest

2014 ◽  
Vol 25 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Andrew T. Schiffmacher ◽  
Rangarajan Padmanabhan ◽  
Sharon Jhingory ◽  
Lisa A. Taneyhill
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Spatiotemporal Pattern ◽  
Cranial Neural Crest ◽  
Mesenchymal Transition ◽  
Crest Cell

The epithelial-to-mesenchymal transition (EMT) is a highly coordinated process underlying both development and disease. Premigratory neural crest cells undergo EMT, migrate away from the neural tube, and differentiate into diverse cell types during vertebrate embryogenesis. Adherens junction disassembly within premigratory neural crest cells is one component of EMT and, in chick cranial neural crest cells, involves cadherin-6B (Cad6B) down-regulation. Whereas Cad6B transcription is repressed by Snail2, the rapid loss of Cad6B protein during EMT is suggestive of posttranslational mechanisms that promote Cad6B turnover. For the first time in vivo, we demonstrate Cad6B proteolysis during neural crest cell EMT, which generates a Cad6B N-terminal fragment (NTF) and two C-terminal fragments (CTF1/2). Coexpression of relevant proteases with Cad6B in vitro shows that a disintegrin and metalloproteinases (ADAMs) ADAM10 and ADAM19, together with γ-secretase, cleave Cad6B to produce the NTF and CTFs previously observed in vivo. Of importance, both ADAMs and γ-secretase are expressed in the appropriate spatiotemporal pattern in vivo to proteolytically process Cad6B. Overexpression or depletion of either ADAM within premigratory neural crest cells prematurely reduces or maintains Cad6B, respectively. Collectively these results suggest a dual mechanism for Cad6B proteolysis involving two ADAMs, along with γ-secretase, during cranial neural crest cell EMT.

scholarly journals Rho-kinase and myosin II affect dynamic neural crest cell behaviors during epithelial to mesenchymal transition in vivo

2008 ◽  
Vol 324 (2) ◽  
pp. 236-244 ◽  
Author(s):  
Jason D. Berndt ◽  
Matthew R. Clay ◽  
Tobias Langenberg ◽  
Mary C. Halloran
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Myosin Ii ◽  
Rho Kinase ◽  
Neural Crest Cell ◽  
Mesenchymal Transition ◽  
Cell Behaviors ◽  
Crest Cell

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 Sip1 mediates an E-cadherin-to-N-cadherin switch during cranial neural crest EMT

2013 ◽  
Vol 203 (5) ◽  
pp. 835-847 ◽  
Author(s):  
Crystal D. Rogers ◽  
Ankur Saxena ◽  
Marianne E. Bronner
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Critical Role ◽  
Embryonic Stem ◽  
Neural Crest Cell ◽  
Stem Cell Population ◽  
Mesenchymal Transition ◽  
E Cadherin

The neural crest, an embryonic stem cell population, initially resides within the dorsal neural tube but subsequently undergoes an epithelial-to-mesenchymal transition (EMT) to commence migration. Although neural crest and cancer EMTs are morphologically similar, little is known regarding conservation of their underlying molecular mechanisms. We report that Sip1, which is involved in cancer EMT, plays a critical role in promoting the neural crest cell transition to a mesenchymal state. Sip1 transcripts are expressed in premigratory/migrating crest cells. After Sip1 loss, the neural crest specifier gene FoxD3 was abnormally retained in the dorsal neuroepithelium, whereas Sox10, which is normally required for emigration, was diminished. Subsequently, clumps of adherent neural crest cells remained adjacent to the neural tube and aberrantly expressed E-cadherin while lacking N-cadherin. These findings demonstrate two distinct phases of neural crest EMT, detachment and mesenchymalization, with the latter involving a novel requirement for Sip1 in regulation of cadherin expression during completion of neural crest EMT.

scholarly journals Connexin 43 impacts the chick premigratory cranial neural crest cell population without affecting the neural crest cell epithelial-to-mesenchymal transition

2019 ◽  
Author(s):  
Karyn Jourdeuil ◽  
Lisa A. Taneyhill
Keyword(s):  
Gap Junctions ◽  
Neural Crest ◽  
Gap Junction ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cranial Neural Crest ◽  
Mesenchymal Transition ◽  
Junction Protein ◽  
Cranial Neural Crest Cells ◽  
Crest Cell

ABSTRACTGap junctions are intercellular channels that allow for the diffusion of small ions and solutes between coupled cells. Connexin 43 (Cx43), also known as Gap Junction Protein α1, is the most broadly expressed gap junction protein in vertebrate development. Cx43 is strongly expressed in premigratory cranial neural crest cells and is maintained throughout the neural crest cell epithelial-to-mesenchymal transition (EMT), but its function in these cells is not known. To this end, we have used a combination of in vivo and ex vivo live imaging with confocal microscopy, immunohistochemistry, and functional assays to assess gap junction formation, and Cx43 function, in chick premigratory cranial neural crest cells. Our results demonstrate that gap junctions exist between chick premigratory and migratory cranial neural crest cells, with Cx43 depletion inhibiting the function of gap junctions. While a reduction in Cx43 levels just prior to neural crest cell EMT did not affect EMT and subsequent emigration of neural crest cells from the neural tube, the size of the premigratory neural crest cell domain was decreased in the absence of any changes in cell proliferation or death. Collectively, these data identify a role for Cx43 within the chick premigratory cranial neural crest cell population prior to EMT and migration.

scholarly journals FGF and retinoic acid activity gradients control the timing of neural crest cell emigration in the trunk

2011 ◽  
Vol 194 (3) ◽  
pp. 489-503 ◽  
Author(s):  
Patricia L. Martínez-Morales ◽  
Ruth Diez del Corral ◽  
Isabel Olivera-Martínez ◽  
Alejandra C. Quiroga ◽  
Raman M. Das ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Epithelial Mesenchymal Transition ◽  
Neural Crest Cell ◽  
Fibroblast Growth ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Morphogenetic Protein ◽  
Trunk Neural Crest ◽  
Crest Cell

Coordination between functionally related adjacent tissues is essential during development. For example, formation of trunk neural crest cells (NCCs) is highly influenced by the adjacent mesoderm, but the molecular mechanism involved is not well understood. As part of this mechanism, fibroblast growth factor (FGF) and retinoic acid (RA) mesodermal gradients control the onset of neurogenesis in the extending neural tube. In this paper, using gain- and loss-of-function experiments, we show that caudal FGF signaling prevents premature specification of NCCs and, consequently, premature epithelial–mesenchymal transition (EMT) to allow cell emigration. In contrast, rostrally generated RA promotes EMT of NCCs at somitic levels. Furthermore, we show that FGF and RA signaling control EMT in part through the modulation of elements of the bone morphogenetic protein and Wnt signaling pathways. These data establish a clear role for opposition of FGF and RA signaling in control of the timing of NCC EMT and emigration and, consequently, coordination of the development of the central and peripheral nervous system during vertebrate trunk elongation.

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