Compartments
Encyclopedia
Compartments can be simply defined as separate, different, adjacent cell populations, which upon juxtaposition, create a lineage boundary. This boundary prevents cell movement
from cells from different lineages across this barrier, restricting them to their compartment. Subdivisions are established by morphogen gradients
and maintained by local cell-cell interaction
s, providing functional units with domains of different regulatory genes
, which give rise to distinct fates
.
Compartment boundaries are found across species
. In the hindbrain
of vertebrate
embryo
s, rhobomeres
are compartments of common lineage outlined by expression of Hox genes. In invertebrate
s, the wing imaginal disc
of Drosophila
provides an excellent model for the study of compartments. Although other tissues
, such as the abdomen, and even other imaginal discs are compartmentalized, much of our understanding of key concepts and molecular mechanisms
involved in compartment boundaries has been derived from experimentation in the wing disc of the fruit fly
.
of these compartments are highly organized and regulated. In addition, this separation creates a region of specialized cells close to the boundary, which serves as a signaling center for the patterning
, polarizing and proliferation
of the entire disc. Compartment boundaries establish these organizing centers by providing the source of morphogen
s that are responsible for the positional information required for development
and regeneration
.
The inability of cell competition to occur across the boundary, indicates that each compartment serves as an autonomous unit of growth
. Differences in growth rates and patterns
in each compartment, maintain the two lineages separated and each control the precise size of the imaginal discs.
of a selector gene
. A selector gene is one that is expressed in one group of cells but not the other, giving the founder cells and their descendants different instructions. Eventually these selector genes become fixed in either an expressed or unexpressed state and are stably inherited
to the descendants, specifying the identity of the compartment and preventing these genetically different cell populations from intermixing. Therefore, these selector genes are key for the formation and maintenance of lineage compartments.
. In the central dogma of compartments, first, morphogen gradients position founder compartment cells. Then, active/inactive selector genes
give a unique genetic identity to cells within a compartment, instructing their fate
and their interactions with the neighboring compartment. Finally, border cells, established by short-range signaling
from one compartment to its neighboring compartment emit long-range signals
that spread to both compartments to regulate the growth
and pattering
of the entire tissue
.
analysis, the Anterior-Posterior boundary was identified. The founder cells, found at the border between parasegments 4 and 5 of embryo
, are already determined at the early blastoderm stage
and defined into the two populations they will generate by stripes of the engrailed gene
.
The selector gene
, engrailed (en)
, is a key determinant
in boundary formation between the anterior and posterior
compartments. As the wing imaginal disc
expands, posterior, but not anterior cells will express engrailed and maintain this expression state as they expand and form the disc. Engrailed mutant clones
of posterior origin will gain anterior affinity and move towards the anterior compartment and intermix with those cells. Within the posterior compartment these clones will sort out and form an ectopic
border where they meet other posterior cells.
Similarly, a clone of anterior cells expressing engrailed will gain posterior identity and create an ectopic boundary where the clone meets other anterior cells in this compartment.
In addition,to its cell autonomous role in specifying
posterior compartment identity, engrailed also has a non-cell autonomous function in the general growth and patterning of the wing disc, through the activation of signaling pathways such as Hedgehog
(Hh) and Decapentaplegic
(Dpp).
The presence of engrailed in the posterior cells leads to the secretion of the short-range inducer Hh which can cross over to the anterior compartment to activate the long-range morphogen, Dpp. Cells in the posterior compartment produce Hh, but only anterior cells can transduce the signal.
Optomotor-blind
(omb) is involved in the transcriptional response of Dpp, which is only required in the anterior cells to interpret Hh signaling for boundary formation and maintenance.
In addition, Cubitus interruptus
(Ci), the signal transducer
of the Hh signal, is expressed throughout the anterior compartment, particularly in anterior border cells. In posterior cells engrailed prevents the expression of Ci, such it is only expressed in anterior cells and hence only these cells can respond to Hh signaling by up-regulating the expression of dpp.
Loss of engrailed function in posterior cells, results in anterior transformation, where Hh expression is decreased and dpp, ci and patched (ptc) is increased, resulting in the formation of a new A/P boundary, suggesting that en positively regulates hh, while negatively regulating ci, ptc and dpp.
hypothesis proposes that these two cell populations express different adhesion molecules
, producing different affinities for each other that minimize their contact.
The selector affinity model proposes that difference in cell affinity between compartments is a result of differential selector gene
expression. The presence or absence of selector genes in a given compartment produces compartment-specific adhesion or recognition molecules that are different from those in its counterpart.
For example, engrailed expressed in the posterior, but not the anterior, cells provides the differential affinity that keeps these compartments separately.
It is also possible that this difference in cell adhesion/affinity is not directly due to en expression, but rather to the ability to receive Hh signaling
. Anterior cells, capable of Hh transduction, will express given adhesive molecules that would differ from those present in posterior cells, creating differential affinity that would prevent them form intermixing.
This signaling-affinity model is supported by experiments that demonstrate the importance of Hh signaling. Clones mutant for the Smoothened (smo)
, the gene responsible for transducing Hh signaling, retain anterior-like features, but move into the posterior compartment without any changes in the expression engrailed or invected. This demonstrates that Hh signaling, rather than the absence of en, is what gives cells their compartmental identity. Nonetheless, this signaling-affinity model is incomplete: smo mutant clones of anterior origin that migrate into the posterior compartment, do not completely associate with these cells, but rather form a smooth boundary with these posterior cells. If signaling-affinity were the only factor determining compartment identity, then these clones, which are no longer receiving Hh signaling, would have the same affinity as the other posterior cells in that compartment and be able to intermix with them.
These experiments indicate that although Hh signaling could be having an effect in adhesive properties, this effect is limited to the border cells rather than throughout both compartments.
It is also possible that both compartments produce the same cell adhesion molecules, but a difference in its abundance or activity could result in sorting between the two compartments. In vitro, transfected cells with high levels of a given adhesion molecule will segregate from cells that expressing lower levels of this same molecule.
Finally, differences in cell bond tension could also play a role in the establishment of the boundary and the separation of the two different cell populations. Experimental data has shown that Myosin-II
is up-regulated along both the dorsal-ventral
and anterior-posterior
boundaries in the imaginal wing disc. The D/V boundary is characterized by the presence of filamentous actin
and mutations in Myosin-II heavy chain
impairs D/V compartmentalization. Similarly, both F-actin and Myosin-II are increased along the A/P boundary, accompanied by a decrease of Bazooka, which was also observed in the D/V border. The Rho-kinase inhibitor Y-27632
, of which Myosin-II is the main target, significantly reduces cell bond tension, suggesting that Myosin-II could be the main effector of this process. In support of the signaling-affinity model, creating an artificial interface between cells with active vs. inactive Hh signaling induces a junctional behavior that aligns the cell bonds of where these opposing cell types meet. Moreover, a 2.5-fold increase in mechanical tension is observed along the A/P boundary, compared to the rest of the tissue. Simulations using a vertex model
demonstrate that this increase in cell bond tension is enough to maintain proliferating cell populations in separate compartment boundaries. Parameters used to measure cell bond tension are based cell-cell adhesion
and cortical tension input.
It has also been suggested that boundary formation is not a result of differential mechanical tension between the two cell populations, but could be a result of the mechanical properties of the boundary itself.
Interestingly, the level the adhesion molecule, E-cadherin
, was unaltered and the biophysical properties of cells between the two compartments were the same. Changes in cell properties, such as an enlarged apical cross-section area, are only observed in anterior and posterior border cells. Along the boundary, orientation of cell division
s was random and there is no evidence that increased cell death
or zones of non-proliferating cells are important for maintaining the A/P or D/V boundary.
to identify molecules regulating differential cell affinity.
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
from cells from different lineages across this barrier, restricting them to their compartment. Subdivisions are established by morphogen gradients
Morphogen
A morphogen is a substance governing the pattern of tissue development, and the positions of the various specialized cell types within a tissue...
and maintained by local cell-cell interaction
Cell-cell interaction
Cell–cell interaction refers to the direct interactions between cells that play a role in the development and function of multicellular organisms....
s, providing functional units with domains of different regulatory genes
Regulator gene
A regulator gene, regulator, or regulatory gene is a gene involved in controlling the expression of one or more other genes. A regulator gene may encode a protein, or it may work at the level of RNA, as in the case of genes encoding microRNAs....
, which give rise to distinct fates
Cell fate determination
Within the field of developmental biology one goal is to understand how a particular cell develops into the final cell type , essentially how a cell’s fate is determined. Within an embryo, 4 processes play out at the cellular and tissue level to essentially create the final organism...
.
Compartment boundaries are found across species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
. In the hindbrain
Rhombencephalon
The rhombencephalon is a developmental categorization of portions of the central nervous system in vertebrates.The rhombencephalon can be subdivided in a variable number of transversal swellings called rhombomeres...
of vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
s, rhobomeres
Rhombomere
In the vertebrate embryo, a rhombomere is a transiently divided segment of the developing neural tube, within the hindbrain region in the area that will eventually become the rhombencephalon. The rhombomeres appear as a series of slightly constricted swellings in the neural tube, caudal to the...
are compartments of common lineage outlined by expression of Hox genes. In invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s, the wing imaginal disc
Imaginal disc
An imaginal disc is one of the parts of a holometabolous insect larva that will become a portion of the outside of the adult insect during the pupal transformation. Contained within the body of the larva, there are pairs of discs that will form, for instance, the wings or legs or antennae or other...
of Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
provides an excellent model for the study of compartments. Although other tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
, such as the abdomen, and even other imaginal discs are compartmentalized, much of our understanding of key concepts and molecular mechanisms
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
involved in compartment boundaries has been derived from experimentation in the wing disc of the fruit fly
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
.
Function
By separating different cell populations, the fateCell fate determination
Within the field of developmental biology one goal is to understand how a particular cell develops into the final cell type , essentially how a cell’s fate is determined. Within an embryo, 4 processes play out at the cellular and tissue level to essentially create the final organism...
of these compartments are highly organized and regulated. In addition, this separation creates a region of specialized cells close to the boundary, which serves as a signaling center for the patterning
Pattern formation
The science of pattern formation deals with the visible, orderly outcomes of self-organisation and the common principles behind similar patterns....
, polarizing and proliferation
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
of the entire disc. Compartment boundaries establish these organizing centers by providing the source of morphogen
Morphogen
A morphogen is a substance governing the pattern of tissue development, and the positions of the various specialized cell types within a tissue...
s that are responsible for the positional information required for development
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
and regeneration
Regeneration (biology)
In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organs, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. At its most...
.
The inability of cell competition to occur across the boundary, indicates that each compartment serves as an autonomous unit of growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
. Differences in growth rates and patterns
Pattern formation
The science of pattern formation deals with the visible, orderly outcomes of self-organisation and the common principles behind similar patterns....
in each compartment, maintain the two lineages separated and each control the precise size of the imaginal discs.
Cell Separation
These two cell populations are kept separate by a mechanism of cell segregation linked to the heritable expressionHeredity
Heredity is the passing of traits to offspring . This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve...
of a selector gene
Homeotic selector gene
Homeotic selector genes confer segment identity in Drosophila. They encode homeodomain proteins which interact with Hox and other homeotic genes to initiate segment-specific gene regulation....
. A selector gene is one that is expressed in one group of cells but not the other, giving the founder cells and their descendants different instructions. Eventually these selector genes become fixed in either an expressed or unexpressed state and are stably inherited
Heredity
Heredity is the passing of traits to offspring . This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve...
to the descendants, specifying the identity of the compartment and preventing these genetically different cell populations from intermixing. Therefore, these selector genes are key for the formation and maintenance of lineage compartments.
Central Dogma
The difference in selector gene activity not only establishes two compartments, but also leads to the formation of a boundary between these two that serves as a source of morphogen gradientsMorphogen
A morphogen is a substance governing the pattern of tissue development, and the positions of the various specialized cell types within a tissue...
. In the central dogma of compartments, first, morphogen gradients position founder compartment cells. Then, active/inactive selector genes
Homeotic selector gene
Homeotic selector genes confer segment identity in Drosophila. They encode homeodomain proteins which interact with Hox and other homeotic genes to initiate segment-specific gene regulation....
give a unique genetic identity to cells within a compartment, instructing their fate
Cell fate determination
Within the field of developmental biology one goal is to understand how a particular cell develops into the final cell type , essentially how a cell’s fate is determined. Within an embryo, 4 processes play out at the cellular and tissue level to essentially create the final organism...
and their interactions with the neighboring compartment. Finally, border cells, established by short-range signaling
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
from one compartment to its neighboring compartment emit long-range signals
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
that spread to both compartments to regulate the growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and pattering
Pattern formation
The science of pattern formation deals with the visible, orderly outcomes of self-organisation and the common principles behind similar patterns....
of the entire tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
.
A/P Boundary
In 1970, by means of clonalClone (cell biology)
A clone is a group of identical cells that share a common ancestry, meaning they are derived from the same mother cell.Clonality implies the state of a cell or a substance being derived from one source or the other...
analysis, the Anterior-Posterior boundary was identified. The founder cells, found at the border between parasegments 4 and 5 of embryo
Drosophila embryogenesis
Drosophila embryogenesis, the process by which Drosophila embryos form, is a favorite model system for geneticists and developmental biologists studying embryogenesis. The small size, short generation time, and large brood size make it ideal for genetic studies. Transparent embryos facilitate...
, are already determined at the early blastoderm stage
Blastoderm
-In amniotes:A blastoderm is the layer of cells formed at one pole of macrolecithal eggs such as the yolky egg of birds. The yolk prevents the division from taking place through the egg, resulting in meroblastic cleavage during the many cleavage divisions...
and defined into the two populations they will generate by stripes of the engrailed gene
Engrailed (gene)
engrailed is a homeodomain transcription factor involved in many aspects of multicellular development. First known for its role in arthropod embryological development, working in consort with the Hox genes, engrailed has been found to be important in other areas of development...
.
The selector gene
Homeotic selector gene
Homeotic selector genes confer segment identity in Drosophila. They encode homeodomain proteins which interact with Hox and other homeotic genes to initiate segment-specific gene regulation....
, engrailed (en)
Engrailed (gene)
engrailed is a homeodomain transcription factor involved in many aspects of multicellular development. First known for its role in arthropod embryological development, working in consort with the Hox genes, engrailed has been found to be important in other areas of development...
, is a key determinant
Cell fate determination
Within the field of developmental biology one goal is to understand how a particular cell develops into the final cell type , essentially how a cell’s fate is determined. Within an embryo, 4 processes play out at the cellular and tissue level to essentially create the final organism...
in boundary formation between the anterior and posterior
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
compartments. As the wing imaginal disc
Imaginal disc
An imaginal disc is one of the parts of a holometabolous insect larva that will become a portion of the outside of the adult insect during the pupal transformation. Contained within the body of the larva, there are pairs of discs that will form, for instance, the wings or legs or antennae or other...
expands, posterior, but not anterior cells will express engrailed and maintain this expression state as they expand and form the disc. Engrailed mutant clones
Clone (cell biology)
A clone is a group of identical cells that share a common ancestry, meaning they are derived from the same mother cell.Clonality implies the state of a cell or a substance being derived from one source or the other...
of posterior origin will gain anterior affinity and move towards the anterior compartment and intermix with those cells. Within the posterior compartment these clones will sort out and form an ectopic
Ectopic expression
Ectopic expression is the expression of a gene in an abnormal place in an organism. This can be caused by a disease, or it can be artificially produced as a way to help determine what the function of that gene is....
border where they meet other posterior cells.
Similarly, a clone of anterior cells expressing engrailed will gain posterior identity and create an ectopic boundary where the clone meets other anterior cells in this compartment.
In addition,to its cell autonomous role in specifying
Regional specification
In the field of developmental biology, regional specification is the process by which different areas are identified in the development of the early embryo. The process by which the cells become specified differs between organisms.-Cell fate determination:...
posterior compartment identity, engrailed also has a non-cell autonomous function in the general growth and patterning of the wing disc, through the activation of signaling pathways such as Hedgehog
Hedgehog signaling pathway
In a growing embryo, cells develop differently in the head or tail end of the embryo, the left or right, and other positions. They also form segments which develop into different body parts. The hedgehog signaling pathway gives cells information that they need to make the embryo develop properly....
(Hh) and Decapentaplegic
Decapentaplegic
Decapentaplegic is a key morphogen involved in the development of the fruit fly Drosophila melanogaster. It is known to be necessary for the correct patterning of the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been...
(Dpp).
The presence of engrailed in the posterior cells leads to the secretion of the short-range inducer Hh which can cross over to the anterior compartment to activate the long-range morphogen, Dpp. Cells in the posterior compartment produce Hh, but only anterior cells can transduce the signal.
Optomotor-blind
Decapentaplegic
Decapentaplegic is a key morphogen involved in the development of the fruit fly Drosophila melanogaster. It is known to be necessary for the correct patterning of the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been...
(omb) is involved in the transcriptional response of Dpp, which is only required in the anterior cells to interpret Hh signaling for boundary formation and maintenance.
In addition, Cubitus interruptus
Ci protein
Ci protein, short for Cubitus interruptus, is a zinc finger containing transcription factor involved in the Hedgehog signaling pathway. In the absence of a signal to the Hedgehog signaling pathway, the Ci protein is cleaved and destroyed in proteasomes...
(Ci), the signal transducer
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
of the Hh signal, is expressed throughout the anterior compartment, particularly in anterior border cells. In posterior cells engrailed prevents the expression of Ci, such it is only expressed in anterior cells and hence only these cells can respond to Hh signaling by up-regulating the expression of dpp.
Loss of engrailed function in posterior cells, results in anterior transformation, where Hh expression is decreased and dpp, ci and patched (ptc) is increased, resulting in the formation of a new A/P boundary, suggesting that en positively regulates hh, while negatively regulating ci, ptc and dpp.
Cell Segregation
To explain how anterior and posterior cells are kept separated, the differential adhesionAdhesion
Adhesion is any attraction process between dissimilar molecular species that can potentially bring them in close contact. By contrast, cohesion takes place between similar molecules....
hypothesis proposes that these two cell populations express different adhesion molecules
Cell adhesion molecule
Cell Adhesion Molecules are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process called cell adhesion....
, producing different affinities for each other that minimize their contact.
The selector affinity model proposes that difference in cell affinity between compartments is a result of differential selector gene
Homeotic selector gene
Homeotic selector genes confer segment identity in Drosophila. They encode homeodomain proteins which interact with Hox and other homeotic genes to initiate segment-specific gene regulation....
expression. The presence or absence of selector genes in a given compartment produces compartment-specific adhesion or recognition molecules that are different from those in its counterpart.
For example, engrailed expressed in the posterior, but not the anterior, cells provides the differential affinity that keeps these compartments separately.
It is also possible that this difference in cell adhesion/affinity is not directly due to en expression, but rather to the ability to receive Hh signaling
Hedgehog signaling pathway
In a growing embryo, cells develop differently in the head or tail end of the embryo, the left or right, and other positions. They also form segments which develop into different body parts. The hedgehog signaling pathway gives cells information that they need to make the embryo develop properly....
. Anterior cells, capable of Hh transduction, will express given adhesive molecules that would differ from those present in posterior cells, creating differential affinity that would prevent them form intermixing.
This signaling-affinity model is supported by experiments that demonstrate the importance of Hh signaling. Clones mutant for the Smoothened (smo)
Smoothened
Smoothened is a G protein-coupled receptor protein encoded by the gene of the hedgehog pathway conserved from flies to humans. It is the molecular target of the teratogen cyclopamine....
, the gene responsible for transducing Hh signaling, retain anterior-like features, but move into the posterior compartment without any changes in the expression engrailed or invected. This demonstrates that Hh signaling, rather than the absence of en, is what gives cells their compartmental identity. Nonetheless, this signaling-affinity model is incomplete: smo mutant clones of anterior origin that migrate into the posterior compartment, do not completely associate with these cells, but rather form a smooth boundary with these posterior cells. If signaling-affinity were the only factor determining compartment identity, then these clones, which are no longer receiving Hh signaling, would have the same affinity as the other posterior cells in that compartment and be able to intermix with them.
These experiments indicate that although Hh signaling could be having an effect in adhesive properties, this effect is limited to the border cells rather than throughout both compartments.
It is also possible that both compartments produce the same cell adhesion molecules, but a difference in its abundance or activity could result in sorting between the two compartments. In vitro, transfected cells with high levels of a given adhesion molecule will segregate from cells that expressing lower levels of this same molecule.
Finally, differences in cell bond tension could also play a role in the establishment of the boundary and the separation of the two different cell populations. Experimental data has shown that Myosin-II
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
is up-regulated along both the dorsal-ventral
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
and anterior-posterior
Anatomical terms of location
Standard anatomical terms of location are designations employed in science that deal with the anatomy of animals to avoid ambiguities that might otherwise arise. They are not language-specific, and thus require no translation...
boundaries in the imaginal wing disc. The D/V boundary is characterized by the presence of filamentous actin
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
and mutations in Myosin-II heavy chain
Myosin-heavy-chain kinase
In enzymology, a myosin-heavy-chain kinase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are ATP and myosin heavy-chain, whereas its two products are ADP and myosin heavy-chain phosphate....
impairs D/V compartmentalization. Similarly, both F-actin and Myosin-II are increased along the A/P boundary, accompanied by a decrease of Bazooka, which was also observed in the D/V border. The Rho-kinase inhibitor Y-27632
Y-27632
Y-27632 is a biochemical tool used in the study of the rho-associated protein kinase signaling pathways. Y-27632 selectively inhibits p160ROCK....
, of which Myosin-II is the main target, significantly reduces cell bond tension, suggesting that Myosin-II could be the main effector of this process. In support of the signaling-affinity model, creating an artificial interface between cells with active vs. inactive Hh signaling induces a junctional behavior that aligns the cell bonds of where these opposing cell types meet. Moreover, a 2.5-fold increase in mechanical tension is observed along the A/P boundary, compared to the rest of the tissue. Simulations using a vertex model
Vertex model
A vertex model is a type of statistical mechanics model in which the Boltzmann weights are associated with a vertex in the model . This contrasts with a nearest-neighbour model, such as the Ising model, in which the energy, and thus the Boltzmann weight of a statistical microstate is attributed to...
demonstrate that this increase in cell bond tension is enough to maintain proliferating cell populations in separate compartment boundaries. Parameters used to measure cell bond tension are based cell-cell adhesion
Adhesion
Adhesion is any attraction process between dissimilar molecular species that can potentially bring them in close contact. By contrast, cohesion takes place between similar molecules....
and cortical tension input.
It has also been suggested that boundary formation is not a result of differential mechanical tension between the two cell populations, but could be a result of the mechanical properties of the boundary itself.
Interestingly, the level the adhesion molecule, E-cadherin
CDH1 (gene)
Cadherin-1 also known as CAM 120/80 or epithelial cadherin or uvomorulin is a protein that in humans is encoded by the CDH1 gene. CDH1 has also been designated as CD324 . It is a tumor suppressor gene.- Function :Cadherin-1 is a classical member of the cadherin superfamily...
, was unaltered and the biophysical properties of cells between the two compartments were the same. Changes in cell properties, such as an enlarged apical cross-section area, are only observed in anterior and posterior border cells. Along the boundary, orientation of cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...
s was random and there is no evidence that increased cell death
Programmed cell death
Programmed cell-death is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process which generally confers advantage during an organism's life-cycle...
or zones of non-proliferating cells are important for maintaining the A/P or D/V boundary.
Future Directions
Despite many attempts to identify the adhesion molecules important for the establishment and maintenance of compartment boundaries, none have been identified. Continuation of our understanding of this process will benefit from further experimental data on cell bonds and cortical tension, as well as screensGenetic screen
A genetic screen is a procedure or test to identify and select individuals who possess a phenotype of interest. A genetic screen for new genes is often referred to as forward genetics as opposed to reverse genetics, the term for identifying mutant alleles in genes that are already known...
to identify molecules regulating differential cell affinity.