Localized distribution of alpha 9 integrin in the cornea and changes in expression during corneal epithelial cell differentiation.

Abstract

A recently characterized integrin alpha-chain, alpha 9, forms heterodimers with the integrin beta 1-chain and is present in the skin with a distribution similar to that of alpha 2 and alpha 3, other beta 1 integrins. To determine whether alpha 9 is expressed in the stratified squamous epithelium of the cornea, we used immunohistochemical techniques to compare the distribution of alpha 9 in the adult mouse cornea with that of alpha 3. Abundant alpha 9 was expressed in the lateral and basal membranes of the basal cells of the conjunctiva and corneal limbus, but very little alpha 9 was present in the basal cells of the central corneal epithelium. In contrast, alpha 3 was present in the membranes of basal cells of the conjunctiva, limbus, and central cornea. To determine when during postnatal maturation of the corneal epithelium alpha 9 becomes restricted to the limbus, we looked at the distribution of alpha 9 and alpha 3 in the developing mouse eye from birth to eyelid opening. At birth, the basal cells of the cornea and developing limbal region did not express alpha 9, but there was abundant alpha 9 expressed in suprabasal cells between the fused lids and in the basal cells of the skin and conjunctiva. In contrast, alpha 3, integrin was expressed uniformly in the basal cells across the surface of the conjunctiva, limbus, and cornea and was present only in the basal cells of the epithelium between the fused eyelids. In the central cornea, alpha 9 expression increased in basal cells up until Day 10 after birth. After Day 10, alpha 9 expression in the central cornea began to decrease; after the lids were open, alpha 9 expression in the central cornea became restricted to the limbus. In the basal and suprabasal cells between the fused eyelids expression of alpha 9 became increasingly restricted over time to the basal cells. Recent data suggest that alpha 9 beta 1 can interact with tenascin. Our dual labeling confocal microscopy studies indicate that localization of alpha 9 and tenascin are not coordinated in the developing mouse cornea. Many recent studies have shown an important role for beta 1 integrins in mediating epithelial cell differentiation in vitro; in vivo, changes in integrin expression have been found in wound healing, psoriasis, and in basal and squamous cell carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)

Niche regulation of corneal epithelial stem cells at the limbus

“…Unlike that of the cornea, the basement membrane of the limbus is undulating with papillae or 'pegs' of stroma extending upward [54] and fenestrated [55,56]; these anatomic features in the limbus suggest that limbal epithelial SCs might closely interact with cells in the underlying limbal stroma (Figure 2). The preferential expression of a9 integrin [19] and N-cadherin [26] without connexin 43 [11] also suggests that limbal SCs interact with unique extracellular components in the niche. Compositionally, other than laminin-1 and laminin-5, the limbal basement membrane also expresses laminin a2b2 chains, while the corneal basement membrane does not.…”

“…In contrast, the SC-containing limbal epithelium has a high proliferative potential in different cultures [12][13][14][15], and their in vitro proliferation is resistant to the inhibition by tumor-promoting phorbol esters [13,16,17]. Furthermore, limbal basal epithelial cells express cytokeratin 19 [18], and integrin a9 [10,19], and preferentially express such progenitor markers as p63 [20], especially its ∆Np63a isoform [21,22], Bcrp1/ABCG2 [10,[23][24][25], and N-cadherin [26].…”

Corneal development associated with eyelid opening

“…The expression and localization of these proteins can be roughly grouped into two categories. In the first group of proteins, which include α-enolase (Chung et al, 1992), α9 integrin (Stepp et al, 1995), and EGF receptor (Zieske and Wasson, 1993), expression is seen in cells across the cornea at the time of birth (Figs. 6 and 7).…”

Ocular surface epithelial and stem cell development

“…When the adult tissue is at steady state, the enzyme α-enolase is present almost exclusively within the limbal basal cells . The cornea and limbus display also distinct patterns of integrin expression (Stepp et al, 1995). The corneal zone expresses a dramatic accumulation of large quantities of globular metabolic enzyme, in particular aldehyde dehydrogenases and transketolase (Abedinia et al, 1990;Sax et al, 1996;Jester et al, 1999).…”