scholarly journals Epigenetic inactivation of miR-203 as a key step in the neural crest epithelial-to-mesenchymal transition

2020 ◽  
Author(s):  
Estefania sanchez vasquez
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Epigenetic Inactivation

scholarly journals Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition

Development ◽  
2019 ◽  
Vol 146 (7) ◽  
pp. dev171017 ◽  
Author(s):  
Estefanía Sánchez-Vásquez ◽  
Marianne E. Bronner ◽  
Pablo H. Strobl-Mazzulla
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Epigenetic Inactivation

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 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.

Mechanisms of Neural Crest Migration

2018 ◽  
Vol 52 (1) ◽  
pp. 43-63 ◽  
Author(s):  
András Szabó ◽  
Roberto Mayor
Keyword(s):  
Neural Crest ◽  
Cell Population ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Embryonic Cell ◽  
Mesenchymal Transition ◽  
Chain Migration ◽  
Mass Migration ◽  
Neural Crest Migration

Neural crest cells are a transient embryonic cell population that migrate collectively to various locations throughout the embryo to contribute a number of cell types to several organs. After induction, the neural crest delaminates and undergoes an epithelial-to-mesenchymal transition before migrating through intricate yet characteristic paths. The neural crest exhibits a variety of migratory behaviors ranging from sheet-like mass migration in the cephalic regions to chain migration in the trunk. During their journey, neural crest cells rely on a range of signals both from their environment and within the migrating population for navigating through the embryo as a collective. Here we review these interactions and mechanisms, including chemotactic cues of neural crest cells’ migration.

scholarly journals The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition

2013 ◽  
Vol 201 (5) ◽  
pp. 759-776 ◽  
Author(s):  
Elias H. Barriga ◽  
Patrick H. Maxwell ◽  
Ariel E. Reyes ◽  
Roberto Mayor
Keyword(s):  
Neural Crest ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cells ◽  
Embryonic Cell ◽  
Zebrafish Embryos ◽  
Mesenchymal Transition ◽  
Metastasis Inhibition ◽  
Neural Crest Migration ◽  
Transcription Factor 1

One of the most important mechanisms that promotes metastasis is the stabilization of Hif-1 (hypoxia-inducible transcription factor 1). We decided to test whether Hif-1α also was required for early embryonic development. We focused our attention on the development of the neural crest, a highly migratory embryonic cell population whose behavior has been likened to cancer metastasis. Inhibition of Hif-1α by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1α controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1α allows cells to initiate migration by promoting the release of cell–cell adhesions. Additionally, Hif-1α controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1α as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells.

scholarly journals A PHD12–Snail2 repressive complex epigenetically mediates neural crest epithelial-to-mesenchymal transition

2012 ◽  
Vol 198 (6) ◽  
pp. 999-1010 ◽  
Author(s):  
Pablo H. Strobl-Mazzulla ◽  
Marianne E. Bronner
Keyword(s):  
Neural Crest ◽  
Adhesion Molecule ◽  
Chromatin Immunoprecipitation ◽  
Epithelial To Mesenchymal Transition ◽  
Adaptor Protein ◽  
Unknown Mechanism ◽  
Mesenchymal Transition ◽  
Histone 3 ◽  
Active Transcription

Neural crest cells form within the neural tube and then undergo an epithelial to mesenchymal transition (EMT) to initiate migration to distant locations. The transcriptional repressor Snail2 has been implicated in neural crest EMT via an as of yet unknown mechanism. We report that the adaptor protein PHD12 is highly expressed before neural crest EMT. At cranial levels, loss of PHD12 phenocopies Snail2 knockdown, preventing transcriptional shutdown of the adhesion molecule Cad6b (Cadherin6b), thereby inhibiting neural crest emigration. Although not directly binding to each other, PHD12 and Snail2 both directly interact with Sin3A in vivo, which in turn complexes with histone deacetylase (HDAC). Chromatin immunoprecipitation revealed that PHD12 is recruited to the Cad6b promoter during neural crest EMT. Consistent with this, lysines on histone 3 at the Cad6b promoter are hyperacetylated before neural crest emigration, correlating with active transcription, but deacetylated during EMT, reflecting the repressive state. Knockdown of either PHD12 or Snail2 prevents Cad6b promoter deacetylation. Collectively, the results show that PHD12 interacts directly with Sin3A/HDAC, which in turn interacts with Snail2, forming a complex at the Cad6b promoter and thus revealing the nature of the in vivo Snail repressive complex that regulates 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.

Sign in / Sign up

Export Citation Format

Share Document