Collagen type VI in neural crest development: Distribution in situ and interaction with cells in vitro

Abstract

We have examined the spatiotemporal distribution of collagen type VI (Col VI) during neural crest development in vivo and its ability to promote neural crest cell attachment and migration in vitro. An affinity purified antiserum and chain-specific monoclonal antibodies against chicken Col VI were employed to immunolocalize the collagen in tissue sections and by immunoblotting. At stages of initial neural crest cell migration, the al(V1) and 012(VI) chains were immunolocalized in apposition with basement membranes of the neural tube, somites, notochord and ectoderm, whereas no immunoreactivity was seen for the cw3(VI) chain. Immunoblotting analysis confirmed the expression of cwl(V1) and a2(VI) chains and the lack of detectable immunoreactivity for the cw3(VI) chain at these early phases of neural crest development. Conversely, at advanced phases of migration and following gangliogenesis, expression of cw3(VI) chain coincided with that of cul(V1) and a2(VI) chains in apposition with basement membranes, around the dorsal root ganglia, and in fibrillar arrangements within the developing dermis and ventral sclerotome. The ability of Col VI to promote neural crest cell attachment and migration was tested in vitro using quantitative assays for these processes. Both native microfilaments and isolated tetramers of Col VI strongly promoted neural crest cell attachment and migration. Optimal stimulation of neural crest cell adhesion and migration was dependent upon structural integrity of Col VI since unfolded and disassembled (Y chains only weakly promoted cell attachment and were virtually inactive in supporting cell movement. The importance of a native macromolecular organization of Col VI further was analyzed in experiments in which dissociated tetramers were reassociated by Ca2+-and temperature-dependent self-aggregation. In contrast to native microfilaments, these oligomeric complexes were less effective in promoting neural crest cell movement, but still retained the ability to stimulate maximal cell attachment. The results indicate that Col VI is a primary component of the extracellular matrix deposited along neural crest migratory pathways, where it mayparticipate in the regulation of cell movement by functioning as a migratory substrate. The ability of Col VI to promote neural crest cell adhesion and motility is highly dependent upon maintainance of a native macromolecular arrangement.0 1993 Wiley-Liss, Inc.

Expression of type VI collagen in the developing mouse heart

“…3). Type VI collagen has been shown to be involved in both the migration and proliferation of cells (Perris et al, 1993;Pfaff et al, 1993;Atkinson et al, 1996). In view of these data, our observations suggest that CT cells synthesize the majority of the type VI collagen present in the AV cushions and that type VI collagen may play a role in modulating normal CT cell migration and proliferation.…”

“…Structural considerations predict that a 1:1:1 [␣1(VI): ␣2(VI): ␣3(VI)] type VI collagen chain assembly is required for the formation of a stable microfibrillar collagen network Heckmann et al, 1992). In vitro studies suggest type VI collagen, in its native state, participates in cell adhesion and migration through interactions with members of the integrin receptor family or the NG2 proteoglycan (Aumailley et al, 1989(Aumailley et al, , 1991Perris et al, 1993;Pfaff et al, 1993;Burg et al, 1996).…”

Association of Type VI Collagen with D-Periodic Collagen Fibrils in Developing Tail Tendons of Mice.

“…The findings support the hypothesis that type VI collagen is present in both filamentous and fibrous matrices, and that networks of type VI collagen may serve as a fine scaffolding that facilitates the integration of types I and III collagen into the developing fibrous matrix. Type VI collagen in developing tissue has also been studied in the neural crest development of the chick embryo (PERRIS et al, 1993), where type VI collagen was described as a primary component of the extracellular matrix deposited along neural crest migratory pathways, or as a migratory substrate. ZHANG et al (1994) have reported the quantification and localization of mRNA for human type VI collagen.…”

Amyloid Precursor-like Protein 2 Promotes Cell Migration toward Fibronectin and Collagen IV

“…In addition to serving a structural role, type IV collagen interactions with cells have been implicated in affecting processes such as cell adhesion, migration, and differentiation (41). Increased levels of type IV collagen are found to occur along certain pathways during development (42,43), tissue remodeling after injury (44,45), and tumor invasion (46,47). In normal adult cornea, ␣3/␣4(IV) chains of collagen IV are found in the epithelial basement membrane (48,49).…”