Fitch John M, Kidder J Michael, Linsenmayer Thomas F
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Dev Dyn. 2005 Jan;232(1):106-18. doi: 10.1002/dvdy.20218.
Avian corneal development requires cellular invasion into the acellular matrix of the primary stroma. Previous results show that this invasion is preceded by the removal of the fibril-associated type IX collagen, which possibly stabilizes matrices through interfibrillar cross-bridges secured by covalent crosslinks. In the present study, we provide evidence for the expression of three matrix metalloproteinases (MMPs) in early corneas, two of which act cooperatively to selectively remove type IX collagen in situ. In organ cultures, MMP inhibitors (either TIMP-2 or a synthetic inhibitor) resulted in arrested development, in which collagen IX persisted, and the stroma remained compact and acellular. We also show that blocking covalent crosslinking of collagen allows for cellular invasion to occur, even when the removal of type IX collagen is prevented. Thus, one factor regulating corneal invasion is the physical structure of the matrix, which can be modified by either selective proteolysis or reducing interfibrillar cross-bridges. We also detected another level of regulation of cellular invasion involving inhibition by the underlying lens. This block, which seems to influence invasive behavior independently of matrix modification, is a transient event that is released in ovo just before invasion proceeds.
鸟类角膜发育需要细胞侵入初级基质的无细胞基质。先前的研究结果表明，这种侵入之前会去除与原纤维相关的IX型胶原蛋白，该胶原蛋白可能通过共价交联固定的原纤维间交联桥来稳定基质。在本研究中，我们提供了早期角膜中三种基质金属蛋白酶（MMPs）表达的证据，其中两种协同作用以选择性地原位去除IX型胶原蛋白。在器官培养中，MMP抑制剂（TIMP-2或合成抑制剂）导致发育停滞，其中IX型胶原蛋白持续存在，并且基质保持紧密且无细胞。我们还表明，即使阻止IX型胶原蛋白的去除，阻断胶原蛋白的共价交联也能使细胞发生侵入。因此，调节角膜侵入的一个因素是基质的物理结构，它可以通过选择性蛋白水解或减少原纤维间交联桥来改变。我们还检测到细胞侵入的另一个调节水平，涉及下方晶状体的抑制作用。这种阻断似乎独立于基质修饰影响侵入行为，是一种在侵入发生前在卵内释放的短暂事件。
