Netrins evoke mixed reactions in motile cells

Like a molecular bulletin board, the extracellular matrix allows indirect communication between cells during development. For posting messages, soluble molecules from various sources are incorporated into more-or-less stable, matrix polymers surrounding tissues and individual cells. Integrins and other cell surface receptors tether these components and coordinate their assembly. Later, for reading messages, cells can express receptors for particular matrix components. In particular, motile cells and axons use matrix cues originating from path or target cells to control their direction and extent of migration. Laminin and netrin Among the oldest and most conserved extracellular matrix proteins are the laminins, which form the basement membranes surrounding epithelia and other tissues, and provide a matrix substrate for various motile and stationary cells. Three homologous subunits, designated alpha , beta and gamma , twine together with their C-termini, and interact with other laminin molecules with their N-termini. A current model is that ternary interactions involving distinct subunits from three different laminin molecules create a quasi-regular, two-dimensional polymer with polarized faces. This scaffold of polymeric laminin supports other matrix molecules and interacts with several integrins and other receptors directly. Specific laminins can stimulate or inhibit cell movement on the basement membrane. Netrins, a family of laminin-related proteins, were discovered in screens of nematode locomotor (uncoordinated, unc) mutants for defective guidance of commissural and motor axons along the dorsoventral body axis, and independently, as soluble factors from floor plate cells responsible for attracting commissural axons towards the ventral midline of the developing spinal cord. From nematodes to vertebrates, these genes are expressed by neuroglia and neurons along the ventral midline of the central nervous system. These netrin cues help attract commissural axons to the ventral midline, and repulse motor and other axons from this same region; moreover, they help to determine the dorsoventral positions of various longitudinal axon tracts. Finally, specific midline neuroglia, neurons, or skeletal muscles might provide localized netrin cues for the major commissures and peripheral nerves, respectively while the C-terminus is unique to netrin. The LN (laminin N-terminal) domain might allow netrin incorporation into basement membranes by co-polymerization with la