Compartment (development) - Cell Segregation

Cell Segregation

To explain how anterior and posterior cells are kept separated, the differential adhesion 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 divisions 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.