Stimulating New Turns

ganglionic eminences within which the internal capsule In this issue of Neuron, a paper by Ming et al. (2001) forms, it is expressed in the eminentia thalami, the enshows that stimulation of action potentials can dramatitopeduncular nucleus, and the caudal ganglionic emically alter the turning responses of growth cones to nence, structures positioned near the more proximal attractive and repulsive guidance factors in culture. part of the path of thalamocortical axons to the neocorTurning up a gradient of netrin-1 is enhanced, myelintex. Therefore, the aberrant thalamocortical projection associated glycoprotein (MAG)–induced repulsive turnin the Tbr1 mutant may be due, at least in part, to the ing is converted to attraction, and Sema3A-induced reloss of potential guidance cues that may normally be pulsive turning is converted to full growth cone collapse. associated with these structures. This study continues a line of investigation that In closing, the study of Hevner et al. has clearly shown opened with the remarkable 1997 discovery from Muthat Tbr1 is essential for several critical early events in ming Poo’s laboratory that attraction can be changed cortical development, including proper lamination and to repulsion in cultured Xenopus spinal neurons by formation of cortical input and output axonal projecchanging cAMP levels pharmacologically (Song et al., tions. In addition, this study has set the stage for impor1997). In a series of subsequent papers, Poo and coltant future work in defining the genes regulated by Tbr1, leagues investigated the basis of this effect (Song and and in sorting out which neurons require cell-autonoPoo, 1999). This has led to a balanced model of turning mous expression of Tbr1 and which neurons require that divides attractants and repellents into two classes Tbr1 nonautonomously for their proper development. based on whether they are influenced by cAMP or cGMP Studies to be done in the coming years should introduce levels. In this model, diffusible factors induce both polyfurther order to the chaotic cortex created by the loss merization (P) and depolymerization (D) of actin. The of Tbr1. P/D ratio determines whether a factor is attractive or