Diffusible signals and fasciculated growth in reticulospinal axon pathfinding in the hindbrain

Abstract

We have addressed the control of longitudinal axon pathfinding in the developing hindbrain, including the caudal projections of reticular and raphe neurons. To test potential sources of guidance signals, we assessed axon outgrowth from embryonic rat hindbrain explants cultured in collagen gels at a distance from explants of midbrain-hindbrain boundary (isthmus), caudal hindbrain, or cervical spinal cord. Our results showed that the isthmus inhibited caudally directed axon outgrowth by 80% relative to controls, whereas rostrally directed axon outgrowth was unaffected. Moreover, caudal hindbrain or cervical spinal cord explants did not inhibit caudal axons. Immunohistochemistry for reticular and raphe neuronal markers indicated that the caudal, but not the rostral projections of these neuronal subpopulations were inhibited by isthmic explants. Companion studies in chick embryos showed that, when the hindbrain was surgically separated from the isthmus, caudal reticulospinal axon projections failed to form and that descending pioneer axons of the medial longitudinal fasciculus (MLF) play an important role in the caudal reticulospinal projection. Taken together, these results suggest that diffusible chemorepellent or nonpermissive signals from the isthmus and substrate-anchored signals on the pioneer MLF axons are involved in the caudal direction of reticulospinal projections and might influence other longitudinal axon projections in the brainstem.

Axon tracts guide zebrafish facial branchiomotor neuron migration through the hindbrain

“…Our approach was similar to methodology previously developed in chick embryos (Hernández-Montiel et al, 2003). We transected the hindbrain of Tg(zCREST1:membRFP) embryos at the r2 level at 14 hpf, a stage that precedes extension of MLF axons into the hindbrain.…”

Longitudinal axons are guided by Slit/Robo signals from the floor plate

“…This suggests that longitudinal trajectories cannot result from net attraction or repulsion from the midline ascending axons in vitro. 6 Other sources of cues may play region-specific roles, such as in the forebrain where local adhesion 7 and diffusible signals 8 influence longitudinal populations. Diffusible Slit repellent signals from the ventral midline have been implicated in guiding forebrain pioneers, 9 project accurately from forebrain to hindbrain tissue, even when intermediate midbrain tissue is deleted.…”

Slit‐Robo signals regulate pioneer axon pathfinding of the tract of the postoptic commissure in the mammalian forebrain

“…Discrete sources of guidance cues in the developing brain control axon growth along longitudinal routes and orchestrate the formation of complex pathways (Erskine et al, 2000; Bagri et al, 2002; Hernandez-Montiel et al, 2003, 2008). In vertebrates, the earliest scaffold of longitudinal axons to form during forebrain development is the tract of the postoptic commissure (TPOC).…”