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Georgia Tech mechanical engineers studied the mechanisms of quail egg epiboly, a developmental process involving mass movement of cells as a sheet, which is linked with medical conditions that include wound healing and cancer. Credit: iStockphoto
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Avian embryos could join the list of model organisms used to study a
specific type of cell migration called epiboly, thanks to the results of a
study published in Developmental Dynamics. The study provides insights
into the mechanisms of epiboly, a developmental process involving mass movement
of cells as a sheet, which is linked with medical conditions that include wound
healing and cancer.
The study explains how epithelial cells expand as a sheet and migrate to
engulf the entire avian egg yolk as it grows. It also reveals the presence of
certain molecules during this process that have not been previously reported in
other major developmental models, including Xenopus frogs and zebrafish.
"These molecules and mechanisms of early development in the avian
embryo may demonstrate evolutionary differences across species in the
collective movement of epithelial cells and motivate additional studies of
avian embryo development," said Evan Zamir, an assistant professor in the
George W. Woodruff School of Mechanical Engineering at Georgia Tech.
Matt Futterman, who worked on the project as a graduate student at Georgia
Tech, and mechanical engineering professor Andrés García also contributed to
this study. The research was funded by Zamir's new faculty support from Georgia
Tech and by a grant to García from the National Institutes of Health.
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Confocal image showing high levels of the protein vimentin (white) at the edge zone of a quail embryo. Cell nuclei are labeled green. Credit: Evan Zamir
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In the study, the researchers conducted immunofluorescence and
high-resolution confocal microscopy experiments to examine the spatial
distribution and expression of five proteins—vimentin, cytokeratin, β-catenin,
E-cadherin, and laminin—as cells moved to wrap the yolk sac of quail embryos
during development.
The results showed that during this process, four of the proteins—vimentin,
cytokeratin, β-catenin, and E-cadherin—appeared in the cells located at the
free edge of the migrating cell sheet. Finding dense interconnected networks of
both vimentin and cytokeratin in the edge cells surprised the researchers.
"Since cytokeratin is generally associated with the epithelial
phenotype and vimentin is generally associated with the mesenchymal phenotype,
it's rare to see them expressed in the same cells, but this does occur in
metastasizing tumor cells," said Zamir.
Cells expressing the mesenchymal phenotype are typically found in connective
tissues, whereas cells of the epithelial phenotype are found in cavities and
glands and on surfaces throughout the body.
This finding provides evidence that epithelial cells normally attached to a
membrane surface underwent biochemical changes that enabled them to assume a
mesenchymal cell phenotype, which enhanced their migratory capacity. This
process, called partial epithelial-to-mesenchymal transition, has many
similarities to the initiation of tumor cell metastasis and wound healing.
Since this epithelial and mesenchymal expression pattern in the edge cells
has not previously been reported in Xenopus or zebrafish, it may be unique to
the avian embryo. This discovery would make the avian embryo a valuable model
for studying tumor cell migration and wound healing.
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Image showing that the edge zone (top of image) of the quail embryo shows no proliferating cells (cyan), unlike the interior zone (bottom of image). Non-proliferating cell nuclei are labeled green. Credit: Evan Zamir
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In addition to detailing protein expression in the quail embryo during
development, the researchers also determined the origin of the new cells
required at the migrating edge to cover the growing yolk. During development,
the radius of the quail yolk doubles every day for the first few days,
representing a hundreds-fold increase in the egg yolk surface area.
"For each individual cell that has to cover the egg yolk as it grows,
the migration around the yolk is extraordinary, because it's such a large
territory—it would be like an ant walking across the earth," explained
Zamir.
Looking more closely at the edge cells, the researchers found strong
evidence that expansion of the edge cell population was due exclusively to
cells relocating from an interior region to the edge as the embryo expanded.
The cells located at the free edge generated the bulk of the traction force
necessary for expansion and towed the cells within the interior of the
epithelium.
"These experiments confirm that edge cell proliferation is not the
primary mechanism for expansion of the edge cell population," noted Zamir.
"And our observation of epithelial-to-mesenchymal transition in the edge
cells explains how these epithelial cells might be changing phenotype to become
migratory in this rapidly expanding sheet."
To determine if this study's findings are indeed unique to the avian embryo,
Zamir plans to conduct further studies to characterize protein expression and
cell migration in Xenopus and zebrafish.
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