RT Journal Article SR Electronic T1 Local Directional Cues Control Growth Polarity of Dopaminergic Axons Along the Rostrocaudal Axis JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4112 OP 4119 DO 10.1523/JNEUROSCI.20-11-04112.2000 VO 20 IS 11 A1 Shin-ichiro Nakamura A1 Yasuko Ito A1 Ryuichi Shirasaki A1 Fujio Murakami YR 2000 UL http://www.jneurosci.org/content/20/11/4112.abstract AB The vertebrate CNS is composed of a variety of longitudinal axonal tracts extending rostrally and caudally. Although recent studies have demonstrated that chemoattraction and chemorepulsion play key roles in axon guidance along the circumferential axis in the neural tube of the vertebrate, mechanisms of axonal elongation along the longitudinal axis, and most importantly, what determines rostrocaudal polarity of axonal growth, remains unknown. Here, we examined the mechanism that guides midbrain dopaminergic axons rostrally, using flat whole-mount preparations of embryonic rat brain both in vivo and in vitro.At embryonic day 11 (E11) and early stage E12, dopaminergic neurons in the ventral midbrain extended short axons dorsally. By middle stage E12, these axons had increased in number, some deflecting rostrally and others caudally. At E13, almost all axons showed rostrally oriented growth heading toward the forebrain targets. In in vitrowhole-mount preparations prepared from an E12 embryo and cultured for 24 hr, these axons showed rostrally oriented growth, but when they were forced to grow on substratum of reversed rostrocaudal polarity, they turned abruptly and grew following the polarity of the reversed midbrain substratum. These results suggest that local directional cues in the midbrain guide these axons rostrally and support the idea that substratum-associated polarized cues play an important role in axon guidance along the longitudinal axis.