Attracted or Repelled? Look Within

branch of the Ig superfamily, but they differ from DCC proteins in the number of extracellular Ig and fibronectin domains and share no similarity over their large cyto-The past several years have seen a revolution in our plasmic domains. Using the well-characterized Dro-understanding of how axons find their targets during sophila midline, Bashaw and Goodman (1999) recog-neural development. These new insights are due in part nized a great opportunity to test in vivo two important to a melding of detailed cellular and genetic character-and related questions: are Netrin and Slit receptors—Fra izations of axon guidance events with the molecular and Robo, respectively—modular such that their cyto-description of several families of phylogenetically con-plasmic domains are responsible for the nature of the served cues capable of mediating these steering deci-growth cone response to a guidance cue; and are attrac-sions (reviewed by Mueller, 1999). Neurons use these tive and repulsive intracellular signaling components cues, which include both attractants and repellents act-generally present in diverse cell types? The answer to ing over short and long distances, to direct their axons both questions is yes. to appropriate intermediate or final targets. Refinement Chimeric Fra or Robo receptors, containing either the of these projections is imparted by the ability of individ-extracellular domain of Fra and the intracellular domain ual axons to respond to multiple guidance cues pre-of Robo (Fra–Robo) or the extracellular domain of Robo sented at different points along their trajectories. Further and the intracellular domain of Fra (Robo–Fra), were complexity in these early guidance events is provided expressed on all neurons in Drosophila embryos. This by the bifunctionality of many of these guidance cues: resulted in repulsive guidance responses to Netrins (Fra– attracting certain populations of axons and repelling Robo) and attractive responses to Slit (Robo–Fra) (see others, or even attracting or repelling the same axon figure, panel A). For example, ectopic Fra–Robo directs depending on the state of certain intracellular signaling axons that would normally cross the midline away from molecules. Though it is likely that many families of guid-it, leading to a commissureless phenotype. In addition, ance cues and their receptors remain to be discovered, Fra–Robo also directs motor axons away from the Net-the tools are now in hand to begin dissecting the molecu-rin-expressing muscles that they would normally inner-lar basis of attractive and repulsive guidance mechanisms. vate. These effects are not likely to be due to dominant-Two studies published in the …