Expression of Crim1 during murine ocular development

Abstract

Crim1 (cysteine-rich motor neuron 1), a novel gene encoding a putative transmembrane protein, has recently been isolated and characterized ( Kolle, G., Georgas, K., Holmes, G.P., Little, M.H., Yamada, T., 2000. CRIM1, a novel gene encoding a cysteine-rich repeat protein, is developmentally regulated and implicated in vertebrate CNS development and organogenesis. Mech. Dev. 90, 181–193). Crim1 contains an IGF-binding protein motif and multiple cysteine-rich repeats, analogous to those of chordin and short gastrulation (sog) proteins that associate with TGFβ superfamily members, namely Bone Morphogenic Protein (BMP). High levels of Crim1 have been detected in the brain, spinal chord and lens. As members of the IGF and TGFβ growth factor families have been shown to influence the behaviour of lens cells (Chamberlain, C.G., McAvoy, J.W., 1997. Fibre differentiation and polarity in the mammalian lens: a key role for FGF. Prog. Ret. Eye Res. 16, 443–478; de Iongh R.U., Lovicu, F.J., Overbeek, P.A., Schneider, M.D., McAvoy J.W., 1999. TGF-β signalling is essential for terminal differentiation of lens fibre cells. Invest. Ophthalmol. Vis. Sci. 40, S561), to further understand the role of Crim1 in the lens, its expression during ocular morphogenesis and growth is investigated. Using in situ hybridisation, the expression patterns of Crim1 are determined in murine eyes from embryonic day 9.5 through to postnatal day 21. Low levels of transcripts for Crim1 are first detected in the lens placode. By the lens pit stage, Crim1 is markedly upregulated with high levels persisting throughout embryonic and foetal development. Crim1 is expressed in both lens epithelial and fibre cells. As lens fibres mature in the nucleus, Crim1 is downregulated but strong expression is maintained in the lens epithelium and in the young fibre cells of the lens cortex. Crim1 is also detected in other developing ocular tissues including corneal and conjunctival epithelia, corneal endothelium, retinal pigmented epithelium, ciliary and iridial retinae and ganglion cells. During postnatal development Crim1 expression is restricted to the lens, with strongest expression in the epithelium and in the early differentiating secondary fibres. Thus, strong expression of Crim1 is a distinctive feature of the lens during morphogenesis and postnatal growth.