scholarly journals How inhibitory cues can both constrain and promote cell migration

2016 ◽  
Vol 213 (5) ◽  
pp. 505-507 ◽  
Author(s):  
Marianne E. Bronner
Keyword(s):  
Mathematical Modeling ◽  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Collective Cell Migration ◽  
Promote Cell Migration ◽  
Neural Crest Migration ◽  
Physical Boundary

Collective cell migration is a common feature in both embryogenesis and metastasis. By coupling studies of neural crest migration in vivo and in vitro with mathematical modeling, Szabó et al. (2016, J. Cell Biol., http://dx.doi.org/10.1083/jcb.201602083) demonstrate that the proteoglycan versican forms a physical boundary that constrains neural crest cells to discrete streams, in turn facilitating their migration.

scholarly journals In vivo confinement promotes collective migration of neural crest cells

2016 ◽  
Vol 213 (5) ◽  
pp. 543-555 ◽  
Author(s):  
András Szabó ◽  
Manuela Melchionda ◽  
Giancarlo Nastasi ◽  
Mae L. Woods ◽  
Salvatore Campo ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Optimal Number ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Extracellular Matrix Molecule ◽  
Experimental Approaches

Collective cell migration is fundamental throughout development and in many diseases. Spatial confinement using micropatterns has been shown to promote collective cell migration in vitro, but its effect in vivo remains unclear. Combining computational and experimental approaches, we show that the in vivo collective migration of neural crest cells (NCCs) depends on such confinement. We demonstrate that confinement may be imposed by the spatiotemporal distribution of a nonpermissive substrate provided by versican, an extracellular matrix molecule previously proposed to have contrasting roles: barrier or promoter of NCC migration. We resolve the controversy by demonstrating that versican works as an inhibitor of NCC migration and also acts as a guiding cue by forming exclusionary boundaries. Our model predicts an optimal number of cells in a given confinement width to allow for directional migration. This optimum coincides with the width of neural crest migratory streams analyzed across different species, proposing an explanation for the highly conserved nature of NCC streams during development.

scholarly journals Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

2013 ◽  
Vol 203 (4) ◽  
pp. 673-689 ◽  
Author(s):  
Ah-Lai Law ◽  
Anne Vehlow ◽  
Maria Kotini ◽  
Lauren Dodgson ◽  
Daniel Soong ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cell ◽  
Direct Interaction ◽  
Dependent Manner ◽  
Border Cell ◽  
Promote Cell Migration ◽  
Wave Complex

Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds active Rac, which regulates a direct interaction between Lpd and the Scar/WAVE complex via Abi. Consequently, Lpd controls lamellipodium size, cell migration speed, and persistence via Scar/WAVE in vitro. Moreover, Lpd knockout mice display defective pigmentation because fewer migrating neural crest-derived melanoblasts reach their target during development. Consistently, Lpd regulates mesenchymal neural crest cell migration cell autonomously in Xenopus laevis via the Scar/WAVE complex. Further, Lpd’s Drosophila melanogaster orthologue Pico binds Scar, and both regulate collective epithelial border cell migration. Pico also controls directed cell protrusions of border cell clusters in a Scar-dependent manner. Taken together, Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo.

Evidence for collapsin-1 functioning in the control of neural crest migration in both trunk and hindbrain regions

Development ◽  
1999 ◽  
Vol 126 (10) ◽  
pp. 2181-2189 ◽  
Author(s):  
B.J. Eickholt ◽  
S.L. Mackenzie ◽  
A. Graham ◽  
F.S. Walsh ◽  
P. Doherty
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cell ◽  
Axon Growth ◽  
Neural Crest Cells ◽  
Neural Crest Cell Migration ◽  
Neural Crest Migration ◽  
Migration Pathways ◽  
Crest Cell

Collapsin-1 belongs to the Semaphorin family of molecules, several members of which have been implicated in the co-ordination of axon growth and guidance. Collapsin-1 can function as a selective chemorepellent for sensory neurons, however, its early expression within the somites and the cranial neural tube (Shepherd, I., Luo, Y., Raper, J. A. and Chang, S. (1996) Dev. Biol. 173, 185–199) suggest that it might contribute to the control of additional developmental processes in the chick. We now report a detailed study on the expression of collapsin-1 as well as on the distribution of collapsin-1-binding sites in regions where neural crest cell migration occurs. collapsin-1 expression is detected in regions bordering neural crest migration pathways in both the trunk and hindbrain regions and a receptor for collapsin-1, neuropilin-1, is expressed by migrating crest cells derived from both regions. When added to crest cells in vitro, a collapsin-1-Fc chimeric protein induces morphological changes similar to those seen in neuronal growth cones. In order to test the function of collapsin-1 on the migration of neural crest cells, an in vitro assay was used in which collapsin-1-Fc was immobilised in alternating stripes consisting of collapsin-Fc/fibronectin versus fibronectin alone. Explanted neural crest cells derived from both trunk and hindbrain regions avoided the collapsin-Fc-containing substratum. These results suggest that collapsin-1 signalling can contribute to the patterning of neural crest cell migration in the developing chick.

scholarly journals MAPRE2 mutations result in altered human cranial neural crest migration, underlying craniofacial malformations in CSC-KT syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cedric Thues ◽  
Jorge S. Valadas ◽  
Liesbeth Deaulmerie ◽  
Ann Geens ◽  
Amit K. Chouhan ◽  
...  
Keyword(s):  
Neural Crest ◽  
Induced Pluripotent Stem Cell ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Cellular Migration ◽  
Cranial Neural Crest ◽  
Craniofacial Malformations ◽  
Neural Crest Migration

AbstractCircumferential skin creases (CSC-KT) is a rare polymalformative syndrome characterised by intellectual disability associated with skin creases on the limbs, and very characteristic craniofacial malformations. Previously, heterozygous and homozygous mutations in MAPRE2 were found to be causal for this disease. MAPRE2 encodes for a member of evolutionary conserved microtubule plus end tracking proteins, the end binding (EB) family. Unlike MAPRE1 and MAPRE3, MAPRE2 is not required for the persistent growth and stabilization of microtubules, but plays a role in other cellular processes such as mitotic progression and regulation of cell adhesion. The mutations identified in MAPRE2 all reside within the calponin homology domain, responsible to track and interact with the plus-end tip of growing microtubules, and previous data showed that altered dosage of MAPRE2 resulted in abnormal branchial arch patterning in zebrafish. In this study, we developed patient derived induced pluripotent stem cell lines for MAPRE2, together with isogenic controls, using CRISPR/Cas9 technology, and differentiated them towards neural crest cells with cranial identity. We show that changes in MAPRE2 lead to alterations in neural crest migration in vitro but also in vivo, following xenotransplantation of neural crest progenitors into developing chicken embryos. In addition, we provide evidence that changes in focal adhesion might underlie the altered cell motility of the MAPRE2 mutant cranial neural crest cells. Our data provide evidence that MAPRE2 is involved in cellular migration of cranial neural crest and offers critical insights into the mechanism underlying the craniofacial dysmorphisms and cleft palate present in CSC-KT patients. This adds the CSC-KT disorder to the growing list of neurocristopathies.

scholarly journals Stretch-induced endogenous electric fields drive neural crest directed collective cell migration in vivo

2021 ◽  
Author(s):  
Fernando Ferreira ◽  
Sofia Moreira ◽  
Elias H Barriga
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Electric Fields ◽  
Embryonic Cell ◽  
Collective Cell Migration ◽  
Convergent Extension ◽  
Topological Features ◽  
Stretch Activated Channels

Directed collective cell migration (dCCM) is essential for morphogenesis. Cell clusters migrate in inherently complex in vivo environments composed of chemical, electrical, mechanical as well as topological features. While these environmental factors have been shown to allow dCCM in vitro, our understanding of dCCM in vivo is mostly limited to chemical guidance. Thus, despite its wide biological relevance, the mechanisms that guide dCCM in vivo remain unclear. To address this, we study endogenous electric fields in relation to the migratory environment of the Xenopus laevis cephalic neural crest, an embryonic cell population that collectively and directionally migrates in vivo. Combining bioelectrical, biomechanical and molecular tools, we show that endogenous electric fields drive neural crest dCCM via electrotaxis in vivo. Moreover, we identify the voltage-sensitive phosphatase 1 (Vsp1) as a key component of the molecular mechanism used by neural crest cells to transduce electric fields into a directional cue. Furthermore, Vsp1 function is specifically required for electrotaxis, being dispensable for cell motility and chemotaxis. Finally, we reveal that endogenous electric fields are mechanoelectrically established. Mechanistically, convergent extension movements of the neural fold generate membrane tension, which in turn opens stretch-activated channels to mobilise the ions required to fuel electric fields. Overall, our results reveal a mechanism of cell guidance, where electrotaxis emerges from the mechanoelectrical and molecular interplay between neighbouring tissues. More broadly, our data contribute to validate the, otherwise understudied, functions of endogenous bioelectrical stimuli in morphogenetic processes.

scholarly journals GSK3 Controls Migration of the Neural Crest Lineage

2018 ◽  
Author(s):  
Sandra G. Gonzalez Malagon ◽  
Anna M. Lopez Muñoz ◽  
Daniel Doro ◽  
Triòna G. Bolger ◽  
Evon Poon ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Glycogen Synthase ◽  
Neuroblastoma Cells ◽  
Neural Crest Cells ◽  
Anaplastic Lymphoma ◽  
Neural Crest Development ◽  
And Migration ◽  
Neural Crest Migration

AbstractMigration of the neural crest lineage is critical to its physiological function. Mechanisms controlling neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here, we uncover novel requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in neural crest cells and that this activation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with pathologically increased ALK activity express high levels of pY-GSK3 and migration of these cells can be inhibited by GSK3 or ALK blockade. In normal neural crest cells, loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK-3 results in failure of migration. All together, this work identifies a role for GSK3 in cell migration during neural crest development and cancer.

scholarly journals Alterations in neural crest migration by a monoclonal antibody that affects cell adhesion.

1985 ◽  
Vol 101 (2) ◽  
pp. 610-617 ◽  
Author(s):  
M Bronner-Fraser
Keyword(s):  
Monoclonal Antibody ◽  
Neural Crest ◽  
Neural Tube ◽  
Rapid Change ◽  
Neural Crest Cells ◽  
Hybridoma Cells ◽  
Perturbation Approach ◽  
Neural Crest Migration

The possible role of a 140-kD cell surface complex in neural crest adhesion and migration was examined using a monoclonal antibody JG22, first described by Greve and Gottlieb (1982, J. Cell. Biochem. 18:221-229). The addition of JG22 to neural crest cells in vitro caused a rapid change in morphology of cells plated on either fibronectin or laminin substrates. The cells became round and phase bright, often detaching from the dish or forming aggregates of rounded cells. Other tissues such as somites, notochords, and neural tubes were unaffected by the antibody in vitro even though the JG22 antigen is detectable in embryonic tissue sections on the surface of the myotome, neural tube, and notochord. The effects of the JG22 on neural crest migration in vivo were examined by a new perturbation approach in which both the antibody and the hybridoma cells were microinjected onto neural crest pathways. Hybridoma cells were labeled with a fluorescent cell marker that is nondeleterious and that is preserved after fixation and tissue sectioning. The JG22 antibody and hybridoma cells caused a marked reduction in cranial neural crest migration, a build-up of neural crest cells within the lumen of the neural tube, and some migration along aberrant pathways. Neural crest migration in the trunk was affected to a much lesser extent. In both cranial and trunk regions, a cell free zone of one or more cell diameters was generally observed between neural crest cells and the JG22 hybridoma cells. Two other monoclonal antibodies, 1-B and 1-N, were used as controls. Both 1-B and 1-N bind to bands of the 140-kD complex precipitated by JG22. Neither control antibody affected neural crest adhesion in vitro or neural crest migration in situ. This suggests that the observed alterations in neural crest migration are due to a functional block of the 140-kD complex.

scholarly journals Self-organized cell migration across scales – from single cell movement to tissue formation

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
pp. dev191767
Author(s):  
Jessica Stock ◽  
Andrea Pauli
Keyword(s):  
Cell Migration ◽  
Multiple Scales ◽  
Single Cells ◽  
Cell Movement ◽  
Biological Response ◽  
Collective Cell Migration ◽  
Theoretical Concepts ◽  
Self Organizing

ABSTRACTSelf-organization is a key feature of many biological and developmental processes, including cell migration. Although cell migration has traditionally been viewed as a biological response to extrinsic signals, advances within the past two decades have highlighted the importance of intrinsic self-organizing properties to direct cell migration on multiple scales. In this Review, we will explore self-organizing mechanisms that lay the foundation for both single and collective cell migration. Based on in vitro and in vivo examples, we will discuss theoretical concepts that underlie the persistent migration of single cells in the absence of directional guidance cues, and the formation of an autonomous cell collective that drives coordinated migration. Finally, we highlight the general implications of self-organizing principles guiding cell migration for biological and medical research.

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