The overall organization of the first tracts in the brain is conserved across vertebrates. These first populations of neurons arise in the fore- and midbrain and extend axons towards the hindbrain of the animal. These longitudinal tracts are established by a simple set of pioneer axons with precise trajectories parallel to the floor plate. How longitudinal axons are to navigate at specific trajectories along the dorsoventral axis has not be studied. To identify the overall role of floor plate tissue was examined in vivo. Ectopic induction or genetic deletion of floor plate diverted longitudinal axons into abnormal trajectories. The expression patterns of the diffusible cues of the Slit family were altered in the floor plate experiments, suggesting their involvement in longitudinal guidance. Slit1; Slit2 double mutants had severe longitudinal errors, particularly for ventral axons, including midline crossing errors and wandering longitudinal trajectories. However, combined Robo1 and Robo2 mutations strongly disrupted each pioneer tract. Thus, pioneer axons depend on long-range floor plate cues, with Slit/Robo signaling required for precise longitudinal trajectories. The phenotypes witnessed in the Slit and Robo double suggested the presence of an additional cue that attracted longitudinal axons towards the floor plate. Netrin1 is a major floor plate attractant, so its function was examined using mutant mice. Loss of Netrin1 resulted in longitudinal axons traveling at an increased distance from the floor plate indicating that Netrin1 is an attractant for longitudinal axons. Quantification of axon trajectories indicated that much of Netrin1 attraction is mediated by the receptor DCC. When taken together, these results indicate that longitudinal axons use a balance of positive and negative cues to navigate along specific trajectories.Major axon guidance cues are expressed in the early brain Several key guidance cues and their receptors have been implicated in one or more of the model systems, and expression appears to be conserved. The ever-expanding sets ofanbsp;...
|Title||:||The Role of the Floor Plate in Longitudinal Axon Guidance|
|Author||:||William Todd Farmer|
|Publisher||:||ProQuest - 2008|