MMP-2 expression during early avian cardiac and neural crest morphogenesis

Abstract

Matrix metalloproteinase-type 2 (MMP-2) degrades extracellular matrix, mediates cell migration and tissue remodeling, and is implicated in mediating neural crest (NC) and cardiac development. However, there is little information regarding the expression and distribution of MMP-2 during cardiogenesis and NC morphogenesis. To elucidate the role of MMP-2, we performed a comprehensive study on the temporal and spatial distribution of MMP-2 mRNA and protein during critical stages of early avian NC and cardiac development. We found that ectodermally derived NC cells did not express MMP-2 mRNA during their initial formation and early emigration but encountered MMP-2 protein in basement membranes deposited by mesodermal cells. While NC cells did not synthesize MMP-2 mRNA early in migration, MMP-2 expression was seen in NC cells within the cranial paraxial and pharyngeal arch mesenchyme at later stages but was never detected in NC-derived neural structures. This suggested NC MMP-2 expression was temporally and spatially dependent on tissue interactions or differed within the various NC subpopulations. MMP-2 was first expressed within cardiogenic splanchnic mesoderm before and during the formation of the early heart tube, at sites of active pharyngeal arch and cardiac remodeling, and during cardiac cushion cell migration. Collectively, these results support the postulate that MMP-2 has an important functional role in early cardiogenesis, NC cell and cardiac cushion migration , and remodeling of the pharyngeal arches and cardiac heart tube. Heart development begins with the formation of cardio-genic fields, specification of the cardiac-cell lineages, and designation of the anterior/posterior and right/left axis of primary heart tube. Endocardial cells and myocardial cells differentiate from splanchnic mesoderm and organize into two primitive heart rudiments that coalesce, forming a single heart tube consisting of endocardium and myocardium separated by extracellular matrix (ECM). This tubular heart loops and is remodeled into an S-shaped tube, while the primitive heart chambers expand and develop muscular septa and trabeculae. In addition, extensive remodeling of the tubular heart aligns the right and left atrioventricular (AV) canals with future left and right ventricles, reshapes the bulboventricular flange, and widens the conus arterio-sus. These remodeling events require extensive modification of both cellular and ECM components. Aside from remodeling, separation of the tubular heart into a four-chambered heart involves the formation of new mesenchymal tissue. The development of the AV septum requires the formation, migration, proliferation, and dif

Diversity in the molecular and cellular strategies of epithelium-to-mesenchyme transitions: Insights from the neural crest

“…55,109 Other studies showed that a subset of NC cells in the hindbrain at the origin of the cardiac NC do not produce MMP-2 by themselves but use for migration MMP-2 released in their environment by mesodermal cells. 110,111 As mentionned before, NC cells also synthesize ADAM proteases such as ADAM-10 in the chick 91 and ADAM-13 in the frog. 112 Furthermore, ADAM-13 has been shown to cleave fibronectin and proposed to facilitate cell migration by reorganizing locally the fibronectin network.…”

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…In addition to the structural rearrangements, delamination of NC cells and active migration throughout the whole embryo involves penetration of the basement membranes and invading extracellular matrices (ECM) (Fig.1 (Cai et al, 2000;Cantemir et al, 2004;Duong and Erickson, 2004). Also expression of several members of the novel metalloproteinase/disintegrin family ADAM identified in cancer have been reported in Xenopus cranial NC cells (Alfandari et al, 2001;Gaultier et al, 2002;Smith et al, 2002;Harrison et al, 2004).…”

MMP‐2 plays an essential role in producing epithelial‐mesenchymal transformations in the avian embryo

“…1d,e,j,n) and some of these cells are apparently neural crest cells, based on HNK-1 labeling or the known location of neural crest cells from chick/quail chimera studies (Fig. 2g-I;Noden, 1982;Lumsden et al, 1991;Cai et al, 2000).…”

“…Several developmental events have been correlated with, or shown to depend on, proteolytic activity, including branching morphogenesis (Talhouk et al, 1991;Sympson et al, 1994;Lim et al, 1995;Lelongt et al, 1997), syntrophoblast invasion of the uterine wall (Harvey et al, 1995;Lefebvre et al, 1995;Alexander et al, 1996), neural crest cell migration (Valinsky and Le Douarin, 1985;Erickson and Isseroff, 1989;Agrawal and Brauer, 1996), endocardial cushion cell migration (McGuire and Orkin, 1992;McGuire and Alexander, 1993;Alexander et al, 1997;Cai et al, 2000), and craniofacial histogenesis (Chin and Werb, 1997).…”