Migration of Melanoblast
In part I, we have reviewed how two types of neural crest cell, neural/glial precursors and melanoblast are differentiated from neural tube. After this process, the neural/glial precursors will migrate ventrolaterally and the melanoblast will migrate dorsolaterally. As we are focused on pigment generation, here we are going to talk about the migration of the melanoblast only.
There are several mechanisms that prevent nonmelanoblast to migrate dorsolaterally, one of them is ephrin. The expression of ephrin in posterior of somite and in dorsolateral pathway excludes the nonmelanoblast neural crest cells and only allows them to enter the anterior part of somite in ventrolateral way. So, why melanoblast can migrate dorsolaterally between the ectoderm and the somite in the presence of ephrin? The key receptor is EphB2 expressed only in melanoblast, which not only allow melanoblast to survive in ephrin, but also act as chemoattractant, to attract melanoblast to migrate dorsolaterally. Another inhibitor of nonmelanoblast is Slits. Similarly, the receptors of Slits, Robo1 and Robo2 in melanoblast allow them to migrate dorsolaterally. It is possible that ephrin and Slits act in conjunctly (Melissa and Carol, 2007). The last inhibiter of nonmelanoblast I want to mention here is endothelin3 (ET3), the ligand of EDNRB2. EDNRB is up regulated in neurons and glial precursors but cannot help them to survive in the presence of ET3. Then, melanoblast down regulates EDNRB and at the same time up regulates EDNRB2. Some experiments have shown that without these inhibitor, nonmelanoblast will migrate dorsolaterally even they do not have these receptors (this receptors act in the role of path finding). Interestingly, although the ligand of EDNRB2 and EphB2 are different, the overexpression of EDNRB2 can maintain normal dorsolateral migration of melanoblast in the absence of EphB2, and vice versa (Melissa, et al., 2008), suggesting they may have overlap in pathway. Other repulsive cues present in the dorsolaterally pathway that restrict the migration of neuronal precursors include spondins, chondroitin sulfate proteoglycans and PNA-binding molecules (Jia, et al., 2005).
In the view of spatial expression, while melanoblast is migrating between ectoderm and dermamyotome, ET3 is expressed in both ectoderm and dermamyotome (Nagy, et al., 2006). But Steel Factor (SLF) only up regulated in dermamyotome after melanoblast are well into the dorsolaterally pathway, at the same time of the expressing of c-KIT in melanoblast (Reedy, 2003). In the mouse, Kit is necessary to maintain the survival of melanoblast, and for their consequent dispersal onto the dorsolaterally pathway (Wehrle-Haller, 2001). But it is different in chickens. c-KIT knocking out does not affect the migration of melanoblast, just affect the maintenance of melanoblast function.
Here I have present the main part of melanoblast migration. Besides, there are some other interesting processes happened during migration, which I will introduce in the following part.
Melissa L. Harris, Ronelle Hall, Carol A. Erickson. Directing pathfinding along the dorsolateral path – the role of EDNRB2 and EphB2 in overcoming inhibition. Development. 2008. 135, 4113-4122
Melissa L. Harris, Carol A. Erickson. Lineage Specification in Neural Crest Cell Pathfinding. Developmental Dynamics. 2007. 236:1–19.
Jia, L., Cheng, L. and Raper, J. Slit/Robo signaling is necessary to confine early neural crest cells to the ventral migratory pathway in the trunk. Dev. Biol. 2005. 282, 411-421.
Nagy, N. and Goldstein, A. M. Endothelin-3 regulates neural crest cell proliferation and differentiation in the hindgut enteric nervous system. Dev. Biol. 2006. 293, 203-217.
Reedy, M. V., Johnson, R. L. and Erickson, C. A. The expression patterns of c-kit and Sl in chicken embryos suggest unexpected roles for these genes in somite and limb development. Gene Expr. 2003. Patterns 3, 53-58.
Wehrle-Haller, B., Meller, M. and Weston, J. A. Analysis of melanocyte precursors in Nf1 mutants reveals that MGF/KIT signaling promotes directed cell migration independent of its function in cell survival. Dev. Biol. 2001. 232, 471-483.