The versatile roles of axon guidance cues in tissue morphogenesis

The Netrin, Slit, Semaphorin, and Ephrin families of secreted proteins were originally characterized in the nervous system as guidance cues for axons; however, recent studies demonstrate that many members of these families contribute to the development of a variety of organs. Here, the current knowledge of their roles is discussed with a focus on four tissues: lung, mammary, cardiovascular, and kidney. While many studies indicate a role for axon guidance cues in regulating cell-cell and cell-extracellular matrix (ECM) interactions during organogenesis, there is accumulating evidence that they also contribute to tissue development by regulating the transcription and translation of genes encoding key morphogenetic factors.