scholarly journals Ptk7 Is Dynamically Localized at Neural Crest Cell–Cell Contact Sites and Functions in Contact Inhibition of Locomotion

2021 ◽  
Vol 22 (17) ◽  
pp. 9324
Author(s):  
Anita Grund ◽  
Katharina Till ◽  
Klaudia Giehl ◽  
Annette Borchers
Keyword(s):  
Neural Crest ◽  
Cell Invasion ◽  
Information Exchange ◽  
Transmembrane Protein ◽  
Ectopic Expression ◽  
Neural Crest Cell ◽  
Contact Inhibition ◽  
Migration And Invasion ◽  
Cell Contact ◽  
Cell Cell

Neural crest (NC) cells are highly migratory cells that contribute to various vertebrate tissues, and whose migratory behaviors resemble cancer cell migration and invasion. Information exchange via dynamic NC cell–cell contact is one mechanism by which the directionality of migrating NC cells is controlled. One transmembrane protein that is most likely involved in this process is protein tyrosine kinase 7 (PTK7), an evolutionary conserved Wnt co-receptor that is expressed in cranial NC cells and several tumor cells. In Xenopus, Ptk7 is required for NC migration. In this study, we show that the Ptk7 protein is dynamically localized at cell–cell contact zones of migrating Xenopus NC cells and required for contact inhibition of locomotion (CIL). Using deletion constructs of Ptk7, we determined that the extracellular immunoglobulin domains of Ptk7 are important for its transient accumulation and that they mediate homophilic binding. Conversely, we found that ectopic expression of Ptk7 in non-NC cells was able to prevent NC cell invasion. However, deletion of the extracellular domains of Ptk7 abolished this effect. Thus, Ptk7 is sufficient at protecting non-NC tissue from NC cell invasion, suggesting a common role of PTK7 in contact inhibition, cell invasion, and tissue integrity.

scholarly journals Cell proliferation drives neural crest cell invasion of the intestine

2007 ◽  
Vol 302 (2) ◽  
pp. 553-568 ◽  
Author(s):  
Matthew J. Simpson ◽  
Dong C. Zhang ◽  
Michael Mariani ◽  
Kerry A. Landman ◽  
Donald F. Newgreen
Keyword(s):  
Cell Proliferation ◽  
Neural Crest ◽  
Cell Invasion ◽  
Neural Crest Cell ◽  
Crest Cell

scholarly journals Crucial and Overlapping Roles of Six1 and Six2 in Craniofacial Development

2019 ◽  
Vol 98 (5) ◽  
pp. 572-579 ◽  
Author(s):  
Z. Liu ◽  
C. Li ◽  
J. Xu ◽  
Y. Lan ◽  
H. Liu ◽  
...  
Keyword(s):  
Neural Crest ◽  
Ectopic Expression ◽  
Mandibular Condyle ◽  
Neural Crest Cell ◽  
Messenger Rnas ◽  
Developmental Defects ◽  
Facial Cleft ◽  
Frontonasal Dysplasia ◽  
Morphogenetic Protein ◽  
Crest Cell

SIX1 and SIX2 encode closely related transcription factors of which disruptions have been associated with distinct craniofacial syndromes, with mutations in SIX1 associated with branchiootic syndrome 3 (BOS3) and heterozygous deletions of SIX2 associated with frontonasal dysplasia defects. Whereas mice deficient in Six1 recapitulated most of the developmental defects associated with BOS3, mice lacking Six2 function had no obvious frontonasal defects. We show that Six1 and Six2 exhibit partly overlapping patterns of expression in the developing mouse embryonic frontonasal, maxillary, and mandibular processes. We found that Six1 –/– Six2 –/– double-mutant mice were born with severe craniofacial deformity not seen in the Six1 –/– or Six2 –/– single mutants, including skull bone agenesis, midline facial cleft, and syngnathia. Moreover, whereas Six1 –/– mice exhibited partial transformation of maxillary zygomatic bone into a mandibular condyle-like structure, Six1 –/–Six2 +/– mice exhibit significantly increased penetrance of the maxillary malformation. In addition to ectopic Dlx5 expression at the maxillary-mandibular junction as recently reported in E10.5 Six1 –/– embryos, the E10.5 Six1 –/– Six2 +/– embryos showed ectopic expression of Bmp4, Msx1, and Msx2 messenger RNAs in the maxillary-mandibular junction. Genetically inactivating 1 allele of either Ednra or Bmp4 significantly reduced the penetrance of maxillary malformation in both Six1 –/– and Six1 –/– Six2 +/– embryos, indicating that Six1 and Six2 regulate both endothelin and bone morphogenetic protein-4 signaling pathways to pattern the facial structures. Furthermore, we show that neural crest–specific inactivation of Six1 in Six2 –/– embryos resulted in midline facial cleft and frontal bone agenesis. We show that Six1 –/– Six2 –/– embryos exhibit significantly reduced expression of key frontonasal development genes Alx1 and Alx3 as well as increased apoptosis in the developing frontonasal mesenchyme. Together, these results indicate that Six1 and Six2 function partly redundantly to control multiple craniofacial developmental processes and play a crucial neural crest cell–autonomous role in frontonasal morphogenesis.

scholarly journals Transcriptome profiling of the branchial arches reveals cell type composition and a conserved signature of neural crest cell invasion

2020 ◽  
Author(s):  
Jason A Morrison ◽  
Rebecca McLennan ◽  
Jessica M Teddy ◽  
Allison R Scott ◽  
Jennifer C Kasemeier-Kulesa ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Invasion ◽  
Neural Crest Cell ◽  
Branchial Arch ◽  
Tissue Growth ◽  
Cell Populations ◽  
Label Free ◽  
Cell Type ◽  
Mesoderm Cell ◽  
Branchial Arches

ABSTRACTThe vertebrate branchial arches that give rise to structures of the head, neck, and heart form with very dynamic tissue growth and well-choreographed neural crest, ectoderm, and mesoderm cell dynamics. Although this morphogenesis has been studied by marker expression and fate-mapping, the mechanisms that control the collective migration and diversity of the neural crest and surrounding tissues remain unclear, in part due to the effects of averaging and need for cell isolation in conventional transcriptome analysis experiments of multiple cell populations. We used label free single cell RNA sequencing on 95,000 individual cells at 2 developmental stages encompassing formation of the first four chick branchial arches to measure the transcriptional states that define the cellular hierarchy and invasion signature of the migrating neural crest. The results confirmed basic features of cell type diversity and led to the discovery of many novel markers that discriminate between axial level and distal-to-proximal cell populations within the branchial arches and neural crest streams. We identified the transcriptional signature of the most invasive neural crest that is conserved within each branchial arch stream and elucidated a set of genes common to other cell invasion signatures in types in cancer, wound healing and development. These data robustly delineate molecularly distinct cell types within the branchial arches and identify important molecular transitions within the migrating neural crest during development.

scholarly journals In ovo time-lapse analysis of chick hindbrain neural crest cell migration shows cell interactions during migration to the branchial arches

Development ◽  
2000 ◽  
Vol 127 (6) ◽  
pp. 1161-1172 ◽  
Author(s):  
P.M. Kulesa ◽  
S.E. Fraser
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Otic Vesicle ◽  
In Ovo ◽  
Branchial Arches ◽  
Neural Crest Cell Migration ◽  
Crest Cell ◽  
Cell Cell

Hindbrain neural crest cells were labeled with DiI and followed in ovo using a new approach for long-term time-lapse confocal microscopy. In ovo imaging allowed us to visualize neural crest cell migration 2–3 times longer than in whole embryo explant cultures, providing a more complete picture of the dynamics of cell migration from emergence at the dorsal midline to entry into the branchial arches. There were aspects of the in ovo neural crest cell migration patterning which were new and different. Surprisingly, there was contact between neural crest cell migration streams bound for different branchial arches. This cell-cell contact occurred in the region lateral to the otic vesicle, where neural crest cells within the distinct streams diverted from their migration pathways into the branchial arches and instead migrated around the otic vesicle to establish a contact between streams. Some individual neural crest cells did appear to cross between the streams, but there was no widespread mixing. Analysis of individual cell trajectories showed that neural crest cells emerge from all rhombomeres (r) and sort into distinct exiting streams adjacent to the even-numbered rhombomeres. Neural crest cell migration behaviors resembled the wide diversity seen in whole embryo chick explants, including chain-like cell arrangements; however, average in ovo cell speeds are as much as 70% faster. To test to what extent neural crest cells from adjoining rhombomeres mix along migration routes and within the branchial arches, separate groups of premigratory neural crest cells were labeled with DiI or DiD. Results showed that r6 and r7 neural crest cells migrated to the same spatial location within the fourth branchial arch. The diversity of migration behaviors suggests that no single mechanism guides in ovo hindbrain neural crest cell migration into the branchial arches. The cell-cell contact between migration streams and the co-localization of neural crest cells from adjoining rhombomeres within a single branchial arch support the notion that the pattern of hindbrain neural crest cell migration emerges dynamically with cell-cell communication playing an important guidance role.

Single-cell reconstruction with spatial context of migrating neural crest cells and their microenvironments during vertebrate head and neck formation

Development ◽  
2021 ◽  
Vol 148 (22) ◽  
Author(s):  
Jason A. Morrison ◽  
Rebecca McLennan ◽  
Jessica M. Teddy ◽  
Allison R. Scott ◽  
Jennifer C. Kasemeier-Kulesa ◽  
...  
Keyword(s):  
Neural Crest ◽  
Head And Neck ◽  
Single Cell ◽  
Cell Invasion ◽  
Spatial Information ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Crest Cell

ABSTRACT The dynamics of multipotent neural crest cell differentiation and invasion as cells travel throughout the vertebrate embryo remain unclear. Here, we preserve spatial information to derive the transcriptional states of migrating neural crest cells and the cellular landscape of the first four chick cranial to cardiac branchial arches (BA1-4) using label-free, unsorted single-cell RNA sequencing. The faithful capture of branchial arch-specific genes led to identification of novel markers of migrating neural crest cells and 266 invasion genes common to all BA1-4 streams. Perturbation analysis of a small subset of invasion genes and time-lapse imaging identified their functional role to regulate neural crest cell behaviors. Comparison of the neural crest invasion signature to other cell invasion phenomena revealed a shared set of 45 genes, a subset of which showed direct relevance to human neuroblastoma cell lines analyzed after exposure to the in vivo chick embryonic neural crest microenvironment. Our data define an important spatio-temporal reference resource to address patterning of the vertebrate head and neck, and previously unidentified cell invasion genes with the potential for broad impact.

scholarly journals Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Conor C. Lynch ◽  
Tracy Vargo-Gogola ◽  
Lynn M. Matrisian ◽  
Barbara Fingleton
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Migration And Invasion ◽  
Cell Contact ◽  
E Cadherin ◽  
Cell Cell

Perturbations in cell-cell contact machinery occur frequently in epithelial cancers and result in increased cancer cell migration and invasion. Previously, we demonstrated that MMP-7, a protease implicated in mammary and intestinal tumor growth, can process the adherens junction component E-cadherin. This observation leads us to test whether MMP-7 processing of E-cadherin could directly impact cell proliferation in nontransformed epithelial cell lines (MDCK and C57MG). Our goal was to investigate the possibility that MMP-7 produced by cancer cells may have effects on adjacent normal epithelium. Here, we show that MMP-7 processing of E-cadherin mediates, (1) loss of cell-cell contact, (2) increased cell migration, (3) a loss of epithelial cell polarization and (4) increased cell proliferation via RhoA activation. These data demonstrate that MMP-7 promotes epithelial cell proliferation via the processing of E-cadherin and provide insights into the molecular mechanisms that govern epithelial cell growth.

scholarly journals Contact-dependent promotion of cell migration by the OL-protocadherin–Nap1 interaction

2008 ◽  
Vol 182 (2) ◽  
pp. 395-410 ◽  
Author(s):  
Shinsuke Nakao ◽  
Anna Platek ◽  
Shinji Hirano ◽  
Masatoshi Takeichi
Keyword(s):  
Transmembrane Protein ◽  
Cell Movement ◽  
Cell Junctions ◽  
Cell Contact ◽  
Actin Assembly ◽  
Exogenous Expression ◽  
Migration Of Cells ◽  
Cadherin Superfamily ◽  
U251 Cells ◽  
Cell Cell

OL-protocadherin (OL-pc) is a transmembrane protein belonging to the cadherin superfamily, which has been shown to accumulate at cell–cell contacts via its homophilic interaction, but its molecular roles remain elusive. In this study, we show that OL-pc bound Nck-associated protein 1 (Nap1), a protein that regulates WAVE-mediated actin assembly. In astrocytoma U251 cells not expressing OL-pc, Nap1 was localized only along the lamellipodia. However, exogenous expression of OL-pc in these cells recruited Nap1 as well as WAVE1 to cell–cell contact sites. Although OL-pc expression had no effect on the motility of solitary U251 cells, it accelerated their movement when they were in contact with one another, causing concomitant reorganization of F-actin and N-cadherin at cell junctions. OL-pc mutants lacking the Nap1-binding site exhibited no such effect. N-cadherin knockdown mimicked OL-pc expression in enhancing cell movement. These results suggest that OL-pc remodels the motility and adhesion machinery at cell junctions by recruiting the Nap1–WAVE1 complex to these sites and, in turn, promotes the migration of cells.

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