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Y. Li, M. Koch, D.D. Hunter, W.J. Brunken; Netrin 4 Expression in Mouse Eye . Invest. Ophthalmol. Vis. Sci. 2005;46(13):594.
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Purpose: Netrins are important developmental cues; they are active in neural guidance and branching epithelial morphogenesis. Netrin 4, a recently described family member, is widely expressed in CNS and somatic tissues, and has been shown expressed by retina by RT–PCR (Koch et al., '00). We are interested in determining the spatial and temporal expression pattern of netrin 4 in the eye. Methods: We used standard immunohistochemical techniques to determine the spatial and temporal expression pattern of netrin 4 in mouse eye. We used Ntn4 null eye as a control. Results: Netrin 4 is developmentally expressed in mouse cornea, lens, retina and optic nerve. And it is located in both basement membrane (BM) and non–basement membrane locations. In cornea, from E12, netrin 4 is found in Bowman’s layer, Descement’s membrane and the corneal stroma; netrin 4 expression dramatically decreases at the junction of corneal and conjunctival epithelia; netrin 4 is not expressed in the palpebrae. In lens, netrin 4 is found in the BM of the lens capsule and is enriched in the posterior capsule. In retina, netrin 4 is found in all the BMs of the retina: inner limiting membrane (ILM), Bruch’s membrane and blood vessel BMs. Interestingly, netrin 4 is expressed in the arteries of the retina and missing from veins. Netrin 4 expression parallels the development of both hyaloid and retinal vessels. In optic nerve, netrin is found in epineurium. In all of these BM sites, netrin 4 expression persists in the adult. In contrast, netrin 4 is expressed transiently in the head of the optic nerve, in association with the glial wedge; this non–basement membrane expression disappears shortly after birth. Conclusions: While netrin 4 is expressed in all tissues of the eye, the spatial restriction (e.g., cornea and arteries) suggests that it may be important in wound healing and vascularization. Its developmental regulation at the head of the optic nerve suggests it plays a role in optic nerve formation. Experiments are underway to test these hypotheses.
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