Abstract
Purpose::
To determine the nature and source of guidance molecules that regulate the trigeminal sensory innervation of the cornea.
Methods::
The expression of the axon repellant molecule, Semaphorin3A (Sema3A) in the eye and its Neuropilin-1 (Npn-1) receptor by the trigeminal ganglion was characterized by insitu hybridization during the development of corneal sensory innervation in chick embryos. Immunostaining of sensory axons was performed on corneas after lens ablation or inhibition of Sema3A in the lens, and on co-cultures of lens vesicles or cornea with trigeminal explants.
Results::
We show that the lens expresses Sema3A and the trigeminal ganglion expresses Npn-1 during cornea innervation. The lens, which immediately underlies the cornea, repels trigeminal axons in vivo and in vitro. Lens ablation results in premature, disorganized innervation of the cornea and disruption of the nerve ring and ventral plexus. This effect is mediated by Sema3A synthesized by the lens interacting with Npn-1 receptors on trigeminal axons. Inhibition of Sema3A-Npn1 signaling abrogates axon repulsion by the lens and cornea in vitro and phenocopies lens removal in vivo.
Conclusions::
These results demonstrate that Sema3A, secreted by the lens, initially repels trigeminal sensory axons from the developing cornea and is necessary for the proper formation of the nerve ring and ventral plexus.
Keywords: cornea: basic science • innervation: sensation • cell-cell communication