Abstract
BackgroundSpinal commissural axons represent a model system for deciphering the molecular logic that regulates the guidance of midline-crossing axons in the developing central nervous system (CNS). Whether the same or specific sets of guidance signals control the navigation of molecularly distinct subtypes of these axons remains an open and largely unexplored question. Although it is well established that post-crossing commissural axons alter their responsiveness to midline-associated guidance cues, our understanding of the repulsive mechanisms that drive the post-crossing segments of these axons away from the midline and whether the underlying guidance systems operate in a commissural axon subtype-specific manner, remains fragmentary at best.ResultsHere, we utilize axonally targeted transgenic reporter mice to visualize genetically distinct dorsal interneuron (dI)1 and dI4 commissural axons and show that the repulsive class 3 semaphorin (Sema3) guidance receptor Neuropilin 2 (Npn2), is selectively expressed on the dI1 population and is required for the guidance of post-crossing dI1, but not dI4, axons. Consistent with these observations, the midline-associated Npn2 ligands, Sema3F and Sema3B, promote the collapse of dI1, but not dI4, axon-associated growth cones in vitro. We also identify, for the first time, a discrete GABAergic population of ventral commissural neurons/axons in the embryonic mouse spinal cord that expresses Npn2, and show that Npn2 is required for the proper guidance of their post-crossing axons.ConclusionsTogether, our findings indicate that Npn2 is selectively expressed in distinct populations of commissural neurons in both the dorsal and ventral spinal cord, and suggest that Sema3-Npn2 signaling regulates the guidance of post-crossing commissural axons in a population-specific manner.
Highlights
Spinal commissural axons represent a model system for deciphering the molecular logic that regulates the guidance of midline-crossing axons in the developing central nervous system (CNS)
To elucidate molecular mechanisms that control the guidance of dI1 and dI4 commissural axons in mammals, we first characterized their trajectories in the spinal cords of Atoh1-tauGFP and Neurog2-tauGFP transgenic mouse lines (Figure 1A)
In sections derived from Neurog2-tauGFP embryos at E11.5 and E12.5, GFP is expressed in dI4 neurons located within a broad domain of the dorsal spinal cord, and their ventrally projecting axons, which extend to, across, and on the contralateral side of the floor plate (FP) (Figure 1 D, E)
Summary
Spinal commissural axons represent a model system for deciphering the molecular logic that regulates the guidance of midline-crossing axons in the developing central nervous system (CNS). An antibody specific for GAD65, a rate-limiting enzyme required for GABA synthesis, labels ventral commissural neurons in the embryonic rat spinal cord [17,18] Together, these markers provide tools for investigating molecular mechanisms that control the guidance of dorsal and ventral commissural axon subtypes. Inhibitory interactions between the Npn receptor and the ventral midlineassociated Sema3s, Sema3B and Sema3F [23,24,25], facilitate the switch in responsiveness exhibited by post-crossing commissural axons [26,27,28,29] It remains to be determined whether Sema3-Npn interactions regulate the pathfinding of all or only specific subsets of commissural axons
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.