Positioning of Cells at their Intrinsic Sites in Multicellular Organisms

Summary Certain types of cell are known to be under bilateral threshold control, e.g., cells receiving a signal of ligands do not respond until the ligand level comes close to a threshold. When the ligand level is around the threshold, the cells adhere to a surface that expresses the ligands, and again do not respond when the ligand level is over the threshold. The bilateral threshold control of membrane-bound ligands (ephrin) and their receptor (Eph) seems to govern positioning of cells at their intrinsic sites. Three examples are shown: (1) In the topographic projection of retinal ganglion axons to the midbrain, the axon terminals expressing Eph receptors crawl on the midbrain surface where the ligand density is graded. The axon terminals find their own sites on the midbrain where the ligand level is at their own threshold. (2) The bilateral threshold control does not only direct positioning of individual cells, but, under assumptions that the cells express ligands and receptors simultaneously in a single cell and the densities of the ligands and the receptors are reciprocal with each other, the bilateral threshold control organizes spontaneously a tissue of graded cell arrangement, which could provide positional information for morphogenesis and regeneration. (3) In a cell aggregate of two types of cells, cells co-expressing ligands and receptors (not necessarily reciprocally) can form curious cell patterns, a checkerboard pattern and a kagome (star) pattern that have been observed on the chick oviduct epithelium.