scholarly journals Supracellular contraction at the rear of neural crest cell groups drives collective chemotaxis

Science ◽  
2018 ◽  
Vol 362 (6412) ◽  
pp. 339-343 ◽  
Author(s):  
Adam Shellard ◽  
András Szabó ◽  
Xavier Trepat ◽  
Roberto Mayor
Keyword(s):  
Neural Crest ◽  
Ex Vivo ◽  
Embryonic Stem ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Stem Cell Population ◽  
Cell Group ◽  
Cell Groups ◽  
Cell Chemotaxis

Collective cell chemotaxis, the directed migration of cell groups along gradients of soluble chemical cues, underlies various developmental and pathological processes. We use neural crest cells, a migratory embryonic stem cell population whose behavior has been likened to malignant invasion, to study collective chemotaxis in vivo. StudyingXenopusand zebrafish, we have shown that the neural crest exhibits a tensile actomyosin ring at the edge of the migratory cell group that contracts in a supracellular fashion. This contractility is polarized during collective cell chemotaxis: It is inhibited at the front but persists at the rear of the cell cluster. The differential contractility drives directed collective cell migration ex vivo and in vivo through the intercalation of rear cells. Thus, in neural crest cells, collective chemotaxis works by rear-wheel drive.

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 A somatic piRNA pathway regulates epithelial-to-mesenchymal transition of chick neural crest cells

2021 ◽  
Author(s):  
Riley Galton ◽  
Katalin Fejes-Toth ◽  
Marianne E. Bronner
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Epithelial To Mesenchymal Transition ◽  
Embryonic Stem ◽  
Neural Crest Cells ◽  
Stem Cell Population ◽  
Small Rna Sequencing ◽  
Mesenchymal Transition ◽  
Sox2 Expression ◽  
Pirna Pathway

AbstractIn the metazoan germline, Piwi proteins play an essential regulatory role in maintenance of stemness and self-renewal by piRNA-mediated repression of transposable elements. To date, the activity of Piwi proteins and the piRNA pathway in vertebrates was believed to be confined to the gonads. Our results reveal expression of Piwil1 in a vertebrate somatic cell type, the neural crest–a migratory embryonic stem cell population. We show that Piwil1 is expressed at low levels throughout chick neural crest development, peaking just before neural crest cells undergo an epithelial-to-mesenchymal transition to leave the neural tube and migrate into the periphery. Importantly, loss of Piwil1 impedes neural crest emigration. Small RNA sequencing reveals somatic piRNAs with sequence signatures of an active ping pong loop. Coupled with Piwil1 knockout RNA-seq, our data suggest that Piwil1 regulates expression of the transposon derived gene ERNI in the chick dorsal neural tube, which in turn suppresses Sox2 expression to precisely control the timing of neural crest specification and emigration. Our work provides mechanistic insight into a novel function of the piRNA pathway as a regulator of somatic development in vertebrates.

scholarly journals From pioneer to repressor: Bimodal foxd3 activity dynamically remodels neural crest regulatory landscape in vivo

2017 ◽  
Author(s):  
Daria Gavriouchkina ◽  
Ruth M Williams ◽  
Martyna Lukoseviciute ◽  
Tatiana Hochgreb-Hägele ◽  
Upeka Senanayake ◽  
...  
Keyword(s):  
Neural Crest ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Stem Cell Population ◽  
Cell Fates ◽  
Developmental Potential ◽  
Regulatory Circuits ◽  
And Migration ◽  
Gene Regulatory Circuits

AbstractThe neural crest (NC) is a transient embryonic stem cell population characterised by its multipotency and broad developmental potential. Here, we perform NC-specific transcriptional and epigenomic profiling of foxd3-mutant versus wild type cells in vivo to define the gene regulatory circuits controlling NC specification. Together with global binding analysis obtained by foxd3 biotin-ChIP and single cell profiles of foxd3-expressing premigratory NC, our analysis shows that during early steps of NC formation, foxd3 acts globally as a pioneer factor to prime the onset of genes regulating NC specification and migration by re-arranging the chromatin landscape, opening cis-regulatory elements and reshuffing nucleosomes. Strikingly, foxd3 then switches from an activator to its canonical role as a transcriptional repressor. Taken together, these results demonstrate that foxd3 acts bimodally in the neural crest as a switch from permissive to repressive nucleosome/chromatin organisation to maintain stemness and define cell fates.

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 Neural crest cells bulldoze through the microenvironment using Aquaporin-1 to stabilize filopodia

2019 ◽  
Author(s):  
Rebecca McLennan ◽  
Mary C. McKinney ◽  
Jessica M. Teddy ◽  
Jason A. Morrison ◽  
Jennifer C. Kasemeier-Kulesa ◽  
...  
Keyword(s):  
Neural Crest ◽  
Protein Function ◽  
Water Channel ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Aquaporin 1 ◽  
Guidance Receptors ◽  
Cranial Neural Crest Cells

ABSTRACTNeural crest migration requires cells to move through an environment filled with dense extracellular matrix and mesoderm to reach targets throughout the vertebrate embryo. Here, we use high-resolution microscopy, computational modeling, and in vitro and in vivo cell invasion assays to investigate the function of Aquaporin-1 (AQP-1) signaling. We find that migrating lead cranial neural crest cells express AQP-1 mRNA and protein, implicating a biological role for water channel protein function during invasion. Differential AQP-1 levels affect neural crest cell speed, direction, and the length and stability of cell filopodia. Further, AQP-1 enhances matrix metalloprotease (MMP) activity and colocalizes with phosphorylated focal adhesion kinases (pFAK). Co-localization of AQP-1 expression with EphB guidance receptors in the same migrating neural crest cells raises novel implications for the concept of guided bulldozing by lead cells during migration.

scholarly journals Theoretical analysis of neural crest cell migration

2020 ◽  
Author(s):  
Hamid Khataee ◽  
Andras Czirok ◽  
Zoltan Neufeld
Keyword(s):  
Neural Crest ◽  
Target Location ◽  
Embryonic Stem ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Open Domain ◽  
Influx Rate ◽  
Neural Crest Cell Migration ◽  
Target Locations ◽  
Crest Cell

AbstractThe neural crest cells are embryonic stem cells that migrate throughout embryos and, at different target locations, give rise to the formation of a variety of tissues and organs. The directional migration of the neural crest cells is experimentally described using a process referred to as contact inhibition of locomotion (CIL), by which cells redirect their movement upon the cell–cell contacts. However, it is unclear how the migration alignment is affected by the motility properties of the cells. Here, we computationally model the migration alignment and the average time to reach a target location as functions of the motility dynamics and interaction of the cells in an open domain with a channel geometry. The results indicate that by varying the properties of the CIL interaction a transition takes place from random movement of the cells to an organized collective migration, where the migration alignment is maximised and the migration time is minimised. This phase transition is accelerated and strengthened with the influx rate of the cells into the domain through increasing the density of the migrating cells. The model further suggests that the migration is more coordinated when the cells with a large CIL radius move fast in a narrow domain.

scholarly journals Genetics Underlying the Interactions between Neural Crest Cells and Eye Development

2020 ◽  
Vol 8 (4) ◽  
pp. 26
Author(s):  
Jochen Weigele ◽  
Brenda L. Bohnsack
Keyword(s):  
Neural Crest ◽  
Anterior Segment ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Eye Diseases ◽  
Stem Cell Population ◽  
Ocular Development ◽  
Early Migration ◽  
Optic Cup ◽  
Crest Cell

The neural crest is a unique, transient stem cell population that is critical for craniofacial and ocular development. Understanding the genetics underlying the steps of neural crest development is essential for gaining insight into the pathogenesis of congenital eye diseases. The neural crest cells play an under-appreciated key role in patterning the neural epithelial-derived optic cup. These interactions between neural crest cells within the periocular mesenchyme and the optic cup, while not well-studied, are critical for optic cup morphogenesis and ocular fissure closure. As a result, microphthalmia and coloboma are common phenotypes in human disease and animal models in which neural crest cell specification and early migration are disrupted. In addition, neural crest cells directly contribute to numerous ocular structures including the cornea, iris, sclera, ciliary body, trabecular meshwork, and aqueous outflow tracts. Defects in later neural crest cell migration and differentiation cause a constellation of well-recognized ocular anterior segment anomalies such as Axenfeld–Rieger Syndrome and Peters Anomaly. This review will focus on the genetics of the neural crest cells within the context of how these complex processes specifically affect overall ocular development and can lead to congenital eye diseases.

scholarly journals Cancer-associated HIF-2α impacts trunk neural crest stemness

2020 ◽  
Author(s):  
Sofie Mohlin ◽  
Camilla U. Persson ◽  
Elina Fredlund ◽  
Emanuela Monni ◽  
Jessica M. Lindvall ◽  
...  
Keyword(s):  
Neural Crest ◽  
Normal Development ◽  
Hypoxia Inducible Factor ◽  
Neural Crest Cells ◽  
Sympathetic Ganglia ◽  
Stem Cell Population ◽  
Neural Crest Development ◽  
Trunk Neural Crest

AbstractThe neural crest is a stem cell population that gives rise to sympathetic ganglia, the cell type of origin of neuroblastoma. Hypoxia Inducible Factor (HIF)-2α is associated with high risk neuroblastoma, however, little is known about its role in normal neural crest development. To address this important question, here we show that HIF-2α is expressed in trunk neural crest cells of human, murine and avian embryos. Modulating HIF-2α in vivo not only causes developmental delays but also induces proliferation and stemness of neural crest cells while altering the number of cells migrating ventrally to sympathoadrenal sites. Transcriptome changes after loss of HIF-2α reflect the in vivo phenotype. The results suggest that expression levels of HIF-2α must be strictly controlled and abnormal levels increase stemness and may promote metastasis. Our findings help elucidate the role of HIF-2α during normal development with implications also in tumor initiation at the onset of neuroblastoma.

Sign in / Sign up

Export Citation Format

Share Document