Temporal and spatial regulation of integrins during development

Abstract

Integrin receptors for extracellular matrix (ECM) are critical determinants of biological processes. Regulation of integrin expression is one way for cells to respond to changes in the ECM, to integrate intracellular signals, and to obtain appropriate adhesion for cell motility, proliferation, and differentiation. Transcriptional and post-translational mechanisms for changing the integrin repertoire at the cell surface have recently been described. These mechanisms work through transcriptional regulation that alters the proportions of one integrin relative to another, referred to as integrin switching, or through localized regulation of integrin-ECM interactions, thus providing exquisite control over cell rearrangements during tissue morphogenesis and remodeling. These integrin regulatory pathways may also be important targets in such emerging fields as tissue engineering and regenerative medicine.

Figure 1. Integrin expression regulates C. elegans gonadogenesis

Relative integrin expression in the DTCs is shown diagrammatically throughout gonadogenesis. DTC positions during migration are noted numerically, 1 – 5, with ina-1 expression in dashed red and pat-2 in yellow. Migration begins at position 1 with high levels of ina-1 expression maintained during ventral movement (2). As the DTC moves from the ventral to dorsal surface (position 2–3), pat-2 is up-regulated. Migration continues along the dorsal surface (4) and ends at position 5 with ina-1 down-regulation. The increase in pat-2 and decrease in ina-1 expression are both regulated by transcription factor vab-3 and are required for proper organ formation [10].

Figure 2. Integrins and ECM in tissue organization

Three examples of adhesion-dependent cell organization during development are shown. (A) Migrating PGCs (red) accumulate along a ribbon of laminin (green) in the E10.5 mouse embryo (Reproduced from [12]; © 1997 The Rockefeller University Press). (B) In the male Drosophila embryo, hub cells (red, arrowheads) localize to the anterior edge of the male gonad (green) (Reproduced from [17], © 2007 Nature Publishing Group). (C) Localized knockdown by injection of α5 integrin morpholinos in a Xenopus embryo (marked by green in ii) results in discontinuous deposition of fibronectin at somite boundaries (anti-fibronectin staining in i and ii (red)) (Reproduced from [19], © 2007 Wiley-Liss, Inc., reprinted with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.).