Epiboly
Encyclopedia
Epiboly is a cell movement that occurs in the early embryo, at the same time as gastrulation
. It is one of many movements in the early embryo that allow for dramatic physical restructuring (see morphogenesis
). The movement is generally characterized as being a thinning and spreading of cell layers. Epiboly has been most extensively studied in zebrafish as their development allows for an easy visualization of the process.
, mesoderm
, and endoderm
). The EVL, YSL, and DEL all undergo epiboly.
Radial intercalation occurs in the DEL. Interior cells of the blastoderm move towards the outer cells, thus "intercalating" with each other. The blastoderm begins to thin as it spreads toward the vegetal pole of the embryo until it has completely engulfed the yolk cell. The EVL also moves vegetally during epiboly, increasing its surface area as it spreads. Work in the ray-finned fish Fundulus
has shown that no large rearrangements occur in the EVL; instead, cells at the leading edge of the EVL align and constrict. The YSL also moves towards the vegetal pole, spreading along the surface of the yolk and migrating slightly ahead of the blastomeres. Once epiboly is complete, the DEL, EVL, and YSL have engulfed the yolk cell, forming a closure known as the blastopore.
demonstrated that the YSL is capable of undergoing epiboly even when the blastoderm has been removed, but that the blastoderm cannot undergo epiboly in the absence of the YSL. In zebrafish, there is a microtubule
array in the yolk that extends from the animal to the vegetal pole of the embryo, and that contracts as epiboly progresses. Treating embryos with the microtubule depolymerizing agent nocodazole
completely blocks epiboly of the YSL and partially blocks epiboly of the blastoderm, while treating with the microtubule stabilizing agent taxol blocks epiboly of all cell layers. There is also evidence for the importance of actin
-based structures in epiboly. Ring-like structures of filamentous actin have been observed at the leading edge of the enveloping layer, where it contacts the yolk cell. It is thought that a network of filamentous actin in the yolk might constrict in a myosin-II dependent manner to close the blastopore at the end of epiboly, via a "purse-string mechanism". Treating embryos with the actin destabilizer cytochalasin b
results in delayed or arrested epiboly.
There is still debate on the extent to which the DEL and EVL epibolic movements are active movements. The EVL contacts the YSL by means of tight junctions. It is thought that these contacts allow the YSL to "tow" the EVL towards the vegetal pole. Claudin
E is a molecule found in tight junctions that appears to be expressed in the EVL and required for normal zebrafish epiboly, supporting this hypothesis. However, zebrafish embryos that fail to make a fully differentiated EVL show defects in epibolic movements of the DEL, EVL, and YSL, suggesting a requirement for a normal EVL for the epiboly of all three cell layers.
The cell-cell adhesion molecule E-cadherin
has been shown to be required for the radial intercalation of the deep cells. Many other molecules involved in cell-cell contact are implicated in zebrafish epiboly, including G alpha (12/13) which interacts with E-Cadherin
and actin
, as well as the cell adhesion molecule EpCam in the EVL, which may modulate adhesion with the underlying deep cells.
Gastrulation
Gastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a trilaminar structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.Gastrulation takes place after cleavage...
. It is one of many movements in the early embryo that allow for dramatic physical restructuring (see morphogenesis
Morphogenesis
Morphogenesis , is the biological process that causes an organism to develop its shape...
). The movement is generally characterized as being a thinning and spreading of cell layers. Epiboly has been most extensively studied in zebrafish as their development allows for an easy visualization of the process.
General movements
Epiboly in zebrafish is the first coordinated cell movement, and begins once the embryo has completed the blastula stage. At this point the zebrafish embryo contains three portions, an epithelial monolayer known as the enveloping layer (EVL), a yolk syncytial layer (YSL) which is a membrane-enclosed group of nuclei that lie on top of the yolk cell, and the deep cells (DEL) of the blastoderm which will eventually form the embryo's three germ layers (ectodermEctoderm
The "ectoderm" is one of the three primary germ cell layers in the very early embryo. The other two layers are the mesoderm and endoderm , with the ectoderm as the most exterior layer...
, mesoderm
Mesoderm
In all bilaterian animals, the mesoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and endoderm , with the mesoderm as the middle layer between them.The mesoderm forms mesenchyme , mesothelium, non-epithelial blood corpuscles and...
, and endoderm
Endoderm
Endoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and mesoderm , with the endoderm as the intermost layer...
). The EVL, YSL, and DEL all undergo epiboly.
Radial intercalation occurs in the DEL. Interior cells of the blastoderm move towards the outer cells, thus "intercalating" with each other. The blastoderm begins to thin as it spreads toward the vegetal pole of the embryo until it has completely engulfed the yolk cell. The EVL also moves vegetally during epiboly, increasing its surface area as it spreads. Work in the ray-finned fish Fundulus
Fundulus
Fundulus is a genus of ray-finned fishes in the superfamily Funduloidea, family Fundulidae . They belong to the order of toothcarps , and therein the large suborder Cyprinodontoidei...
has shown that no large rearrangements occur in the EVL; instead, cells at the leading edge of the EVL align and constrict. The YSL also moves towards the vegetal pole, spreading along the surface of the yolk and migrating slightly ahead of the blastomeres. Once epiboly is complete, the DEL, EVL, and YSL have engulfed the yolk cell, forming a closure known as the blastopore.
Cytoskeletal and cell adhesion components
Completion of epiboly requires the coordination of cytoskeletal changes across the embryo. The YSL appears to play a prominent role in this process. Studies on FundulusFundulus
Fundulus is a genus of ray-finned fishes in the superfamily Funduloidea, family Fundulidae . They belong to the order of toothcarps , and therein the large suborder Cyprinodontoidei...
demonstrated that the YSL is capable of undergoing epiboly even when the blastoderm has been removed, but that the blastoderm cannot undergo epiboly in the absence of the YSL. In zebrafish, there is a microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
array in the yolk that extends from the animal to the vegetal pole of the embryo, and that contracts as epiboly progresses. Treating embryos with the microtubule depolymerizing agent nocodazole
Nocodazole
Nocodazole is an anti-neoplastic agent which exerts its effect in cells by interfering with the polymerization of microtubules. Microtubules are one type of fibre which constitutes the cytoskeleton, and the dynamic microtubule network has several important roles in the cell, including vesicular...
completely blocks epiboly of the YSL and partially blocks epiboly of the blastoderm, while treating with the microtubule stabilizing agent taxol blocks epiboly of all cell layers. There is also evidence for the importance of actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
-based structures in epiboly. Ring-like structures of filamentous actin have been observed at the leading edge of the enveloping layer, where it contacts the yolk cell. It is thought that a network of filamentous actin in the yolk might constrict in a myosin-II dependent manner to close the blastopore at the end of epiboly, via a "purse-string mechanism". Treating embryos with the actin destabilizer cytochalasin b
Cytochalasin B
Cytochalasin B is a cell-permeable mycotoxin. It inhibits cytoplasmic division by blocking the formation of contractile microfilaments. It inhibits cell movement and induces nuclear extrusion. Cytochalasin B shortens actin filaments by blocking monomer addition at the fast-growing end of polymers....
results in delayed or arrested epiboly.
There is still debate on the extent to which the DEL and EVL epibolic movements are active movements. The EVL contacts the YSL by means of tight junctions. It is thought that these contacts allow the YSL to "tow" the EVL towards the vegetal pole. Claudin
Claudin
Claudins are a family of proteins that are the most important components of the tight junctions, where they establish the paracellular barrier that controls the flow of molecules in the intercellular space between the cells of an epithelium...
E is a molecule found in tight junctions that appears to be expressed in the EVL and required for normal zebrafish epiboly, supporting this hypothesis. However, zebrafish embryos that fail to make a fully differentiated EVL show defects in epibolic movements of the DEL, EVL, and YSL, suggesting a requirement for a normal EVL for the epiboly of all three cell layers.
The cell-cell adhesion molecule E-cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...
has been shown to be required for the radial intercalation of the deep cells. Many other molecules involved in cell-cell contact are implicated in zebrafish epiboly, including G alpha (12/13) which interacts with E-Cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...
and actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
, as well as the cell adhesion molecule EpCam in the EVL, which may modulate adhesion with the underlying deep cells.