Thus, Drosophila Slit binds cells expressing either rRobo1 or rRobo2, and hSlit2 binds cells expressing dRobo1, although these interactions appeared weaker than those observed within species. This prompted an examination of whether Slit proteins can also bind laminins. Since Netrin proteins show homology to a portion of the laminin molecule, whether Netrin 1 and Slit2 can bind one another was examined. To determine if attraction versus repulsion is a modular function encoded in the cytoplasmic domain of these receptors, chimeras were created carrying the ectodomain of one receptor and the cytoplasmic domain of the other and their function in transgenic Drosophila was tested. In Drosophila, the same midline cells normally secrete both Netrins and Slit.
Growth cones can simultaneously respond to both ligands in a cell-specific fashion.
Some growth cones express high levels of Fra and low levels of Robo, and they extend toward and across the midline. Other growth cones appear to express high levels of both receptors, and they can extend toward the midline, but they do not cross it. Such complex and dynamic behavior requires growth cones to be able to simultaneously respond to both attractants and repellents and to integrate these signals and respond to the relative balance of forces. Introducing a chimeric receptor into this finely tuned system leads to dramatic phenotypes. Adding a receptor that responds to Netrin as a repellent leads to a comm -like phenotype in which too few axons cross the midline.