Cellular and molecular partners involved in gut morphogenesis and differentiation

Abstract

The intestinal mucosa represents an interesting model to study the cellular and molecular basis of epithelial^mesenchymal cross-talk participating in the development and maintenance of the digestive function. This cross-talk involves extracellular matrix molecules, cell^cell and cell^matrix adhesion molecules as well as paracrine factors and their receptors. The cellular and molecular unit is additionally regulated by hormonal, immune and neural inputs. Such integrated cell interactions are involved in pattern formation, in proximodistal regionalization, in maintenance of a gradient of epithelial proliferation and di¡erentiation, and in epithelial cell migration.We focus predominantly on two aspects of these integrated interactions in this paper: (i) the role of basement membrane molecules, namely laminins, in the developmental and spatial epithelial behaviour; and (ii) the importance of the mesenchymal cell compartment in these processes.

Epithelial organization and cyst lumen expansion require efficient Sec13–Sec31-driven secretion

“…A dynamic interplay between both epithelial and surrounding cells in terms of ECM deposition and remodelling is certainly necessary to direct morphogenesis in vivo (Kedinger et al, 1998;Simon-Assmann et al, 1998;O'Brien et al, 2001;MartinBelmonte et al, 2008). The difference in ECM composition surrounding Sec13-depleted cysts could be either due to a selective defect in secretion, or impaired matrix assembly.…”

Niche regulation of corneal epithelial stem cells at the limbus

“…npg basement membrane, while a3 and a5 chains are in the corneal counterpart [57,58]. These limbal basement membrane components might help determine SC distribution in the niche as suggested in the intestinal crypt villus (for review, see [59]). Furthermore, like that of other SC niches [60,61], the limbal basement membrane might help sequester and hence modulate concentrations of growth factors and cytokines that are released from limbal niche cells for efficient and precise targeting onto limbal SCs.…”

Polyps as biomarkers for colorectal neoplasia

“…The findings of genetic markers specific for hamartomatous polyps of the familial syndromes of juvenile polyposis (12)(13)(14)(15) and Peutz Jegher Syndromes (16), conditions associated with considerable CRC risk, suggests that other complementary pathways exist through which neoplasia may progress. The genetic aberrations in these syndromes abide not in the epithelial component, but in the mesenchymal tissue, suggesting some biochemical "crosstalk" between the epithelial component and the matrix (17,18), long-recognized but heretofore ill-defined. These findings have ushered in the concept of "landscaper" genes (15) which may prepare the milieu for progress of the carcinogenic process (table 1).…”