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The Specificity of the Extracellular Matrix

Before the molecular analysis of the migratory pathway of the neural crest cells was possible, a series of ingenious experiments demonstrated that the extracellular matrix regulated neural crest cell migration.Some of the best evidence for the importance of extracellular matrices in directing neural crest cell migration comes from studies of mutant salamanders. There exists in some axolotl salamanders a mutation wherein the neural crest forms, but its cells fail to migrate along the dorsolateral pathway. This is most readily seen in the lack of pigment cells anywhere except atop the neural tube of these animals (Figure 1), and these cells eventually degenerate. When wild-type neural crests are transplanted into mutant embryos, the crest cells are unable to migrate. However, when crests from mutant embryos are transplanted into wild-type embryos, their cells migrate normally (Spieth and Keller, 1986). Thus, the defect in this mutant is in the environment that the cells encounter, not in the cells themselves. (The road is deficient, not the vehicle.) Löfberg and co-workers (1989) used this information to show that the extracellular matrix contains critical components regulating neural crest cell migration. They absorbed, onto membrane microcarriers, extracellular matrix from the subepidermal region of the skin (through which the pigment-forming neural crest cells would migrate). They then placed these microcarriers next to the neural crests of mutant and wild-type embryos just before migration would occur. The microcarriers alone did not stimulate migration from either wild-type or mutant crests (Figure 2A, B). Microcarriers containing extracellular matrix material from mutant embryos likewise did not stimulate neural crest cell migration in either mutant or wild-type embryos (Figure 2C, D). The microcarriers containing wild-type extracellular matrix, however, were able to stimulate neural crest migration from both the mutant and wild-type crests (Figure 2E, F), demonstrating the importance of the extracellular matrix in neural crest cell migration.

Figure 1
Figure 1   Deficiency of neural crest cell migration in the d/d mutant of the axolotl. The larvae of wild-type axolotls (A) are characterized by pigment cells throughout the body, except for the most ventral portions. (B) In the d/d mutant, the neural crest-derived pigment cells form a stripe along the dorsal midline of the larva. Scanning electron micrographs of the embryonic neural crest shows that the neural crest cells of the wild-type embryos (C) migrate over the neural tube into the somites, while those crest cells of the mutant (D) remain atop the neural tube. (From Löfberg et al., 1989; photographs courtesy of the authors.)

Figure 2
Figure 2   mportance of the extracellular matrix in neural crest cell migration. These diagrams represent the transplantation experiments wherein extracellular matrix components were carried between wild-type (dark) and mutant (color) donor and host embryos. The upper row represents the donor embryos, while the lower line shows the wild-type and mutant hosts into which the matrix-bearing microcarriers were added. The stimulation denotes the number of times that neural crest cells were seen migrating from the crest in the region of the microcarrier. (After Löfberg et al., 1989.)

Literature Cited

Löfberg, J., Perris, R., and Epperlin, H. H. 1989. Timing in the regulation of neural crest cell migration: Retarded maturation of regional extracellular matrix inhibits pigment cell migration in embryos of the white axolotl mutant. Dev. Biol 131: 168-181.

Spieth, J., and Keller, R. E. 1984. Neural crest cell behavio in white and dark larvae of Ambystoma mexicanum: Differences in cell morphology, arrangement and extracellular matrix as related to migration. J. Exp. Zool. 229: 91-107.

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