[
J Exp Zool,
1999]
A memorable workshop, focused on causal mechanisms in metazoan evolution and sponsored by NASA, was held in early June 1998, at MBL. The workshop was organized by Mike Levine and Eric H. Davidson, and it included the PI and associates from 12 different laboratories, a total of about 30 people. Each laboratory had about two and one half hours in which to represent its recent research and cast up its current ideas for an often intense discussion. In the following we have tried to enunciate some of the major themes that emerged, and to reflect on their implications. The opinions voiced are our own. We would like to tender apologies over those contributions we have not been able to include, but this is not, strictly speaking, a meeting review. Rather we have focused on those topics that bear more directly on evolutionary mechanisms, and have therefore slighted some presentations (including some of our own), that were oriented mainly toward developmental processes. J. Exp. Zool. (Mol. Dev. Evol. ) 285:104-115, 1999.
[
Dev Biol,
2008]
One of the challenges to understanding nervous system development has been to establish how a fairly limited number of axon guidance cues can set up the patterning of very complex nervous systems. Studies on organisms with relatively simple nervous systems such as Drosophila melanogaster and C. elegans have provided many insights into axon guidance mechanisms. The axons of many neurons migrate along both the dorsal-ventral axis (DV) and the anterior-posterior (AP) at different phases of development, and in addition they may also cross the midline. Axon migration in the dorsal-ventral (DV) direction is mainly controlled by Netrins with their receptors; UNC-40/DCC and UNC-5, and the Slits with their receptors; Robo/SAX-3. Axon guidance in the anterior-posterior (AP) axis is mainly controlled by Wnts with their receptors; the Frizzleds/Fz. An individual axon may be subjected to opposing attractive and repulsive forces coming from opposite sides in the same axis but there may also be opposing cues in the other axis of migration. All the information from the cues has to be integrated within the growth cone at the leading edge of the migrating axon to elicit a response. Recent studies have provided insight into how this is achieved. Evidence suggests that the axis of axon migration is determined by the manner in which Netrin, Slit and Wnt receptors are polarized (localized) within the neuron prior to axon outgrowth. The same molecules are involved in both axon outgrowth and axon guidance, for at least some neurons in C. elegans, whether the cue is the attractive cue UNC-6/Netrin working though UNC-40/DCC or the repulsive cue SLT-1/Slit working though the receptor SAX-3/Robo (Adler et al., 2006, Chang et al., 2006, Quinn et al., 2006, 2008). The molecules involved in cell signaling in this case are polarized within the cell body of the neuron before process outgrowth and direct the axon outgrowth. Expression of the Netrin receptor UNC-40/DCC or the Slit receptor SAX-3/Robo in axons that normally migrate in the AP direction causes neuronal polarity reversal in a Netrin and Slit independent manner (Levy-Strumpf and Culotti 2007, Watari-Goshima et al., 2007). Localization of the receptors in this case is caused by the kinesin-related VAB-8L which appears to govern the site of axon outgrowth in these neurons by causing receptor localization. Therefore, asymmetric localization of axon guidance receptors is followed by axon outgrowth in vivo using the receptor''s normal cue, either attractive, repulsive or unknown cues.