Brief Review of Pigment Generation, Part III (BIOL 5104 blog 7)

Migration of Melanoblast (continued)

In Xenopus embryo, contact inhibition of locomotion was found happens during neural crest cell migration. When two migrating neural crest cells meet, they stop, collapse their protrusions and change direction. In contrast, when a neural crest cell meets another cell type, it fails to display contact inhibition of locomotion; instead, it invades the other tissue, like metastatic cancer cells. Inhibition of non-canonical Wnt signaling abolishes both contact inhibition of locomotion and the directionality of neural crest migration. Wnt signalling members localise at the site of cell contact, leading to activation of RhoA in this region. This contact inhibition of locomotion should be present in any species and breeds which have uniformly distributed pigmentation. But the I still don’t know whether this in chicken is similar like this in Xenopus.

Recently, two distinct types of melanocyte are described in mice, dermal (non-cutaneous) melanocytes and epidermal melanocytes (Aoki, et al., 2009). Experiments have shown that ectopically expression of Endothelin 3 (EDN3) affect the dermal pigmentation but not the hair color (Garcia, et al., 2008). These non-cutaneous like dermal melanocytes are incapable of contributing to epidermal hair follicle pigmentation further highlighting the functional differences between these two melanocyte populations (Aoki, et al., 2011). Similar dermal pigmentation phenotype is seen when EDN3 is ectopically expressed in the chicken, which is called dermal hyperpigmentation or Fibromelanosis (FM), a breed character of Silkie chickens. EDN3 is up regulated in Silkie chicken during migration of melanoblast and even in the adult Silkie chicken skin tissue. But Silkie expressing FM can be white in feather (so called feather, it looks like mammals hair or chick’s down) and also can be other feather color, which indicates that FM does not affect feather pigmentation (Dorshorst, et al., 2011). Previous studies have shown that in avian, EDN3 exerts trophic, mitogenic and melanogenesis-promoting activities on early neural crest cells in culture. EDN3-responsive precursors were identified in neural crest clonal cultures and include fate-restricted glial and melanocytic cells as well as bipotent glia–melanocyte (GM) precursors. The GM progenitor is thus a main target of survival and mitogenic activities of EDN3. Experiments have shown that EDN3 appeared capable for transition between glia and melanocytes in vitro (Douarin and Dupin, 2003). But it seems like glia, or at least its function, is not affected by high expression of in EDN3 Silkie chicken. The explanation need to be further investigated.

When we are talking about FM in Silkie, we have to mention another gene, inhibitor of dermal melanin (Id). The phenotype of Id gene is the abnormal migration of melanoblast, which will invade into the ventral pathway normally reserved for neuronal and glial cell lineages. So, Id causes pigmentation of internal connective tissue and the exterior (Dorshorst, et al., 2010). Similar like inhibitors prevent glial cell entering dorsolaterally pathway, something called barrier molecules (PNA-binding molecules) can stop melanoblast to migrate ventrolaterally. But what the barrier molecules exactly are is still unknown, we can only label them by PNA (Lection Peanut Agglutinin). In this way, we can know the distribution of barrier molecules is normal in Silkie during most of the time of melanoblast migration. But in later stage, they disappear and then melanoblast migrates from the dorsolateral space to the ventral part. So, the melanoblast in the ventral part is not because of their migration in the same way as the neural/glial precursors at the beginning. Some other experiments have shown that the abnormal migration of melanoblast is not an autonomous property of Silkie neural crest, but the environment difference around the pathways, which consists with previous observation of PNA-binding molecules’ down regulation (Faraco, et al., 2001).

The identification of the barrier molecules and the detail mechanism of Id gene will give us better understanding about neural crest cells’ path finding.


Carlos Carmona-Fontaine, Helen K. Matthews, Sei Kuriyama, Mauricio Moreno, Graham A. Dunn, Maddy Parsons, Claudio D. Stern, and Roberto Mayor. Contact Inhibition of Locomotion in vivo controls neural crest directional migration, Nature. 2008 December 18; 456(7224): 957–961.

Aoki H, Yamada Y, Hara A, Kunisada T. Two distinct types of mouse melanocyte: differential signaling requirement for themaintenance of non-cutaneous and dermal versus epidermal melanocytes. Development. 2009. 136: 2511–2521.

Garcia RJ, Ittah A, Mirabal S, Figueroa J, Lopez L, et al. Endothelin 3 induces skin pigmentation in a keratin-driven inducible mouse model. J Invest Dermatol. 2008. 128: 131–142.

Aoki H, Hara A, Motohashi T, Osawa M, Kunisada T. Functionally distinct melanocyte populations revealed by reconstitution of hair follicles in mice. Pigment Cell Melanoma Res. 2011. 24: 125–135.

Ben Dorshorst, Anna-Maja Molin, Carl-Johan Rubin, Anna M. Johansson, Lina Stromstedt, Manh-Hung Pham, Chih-Feng Chen, Finn Hallbook, Chris Ashwell, Leif Andersson. A Complex Genomic Rearrangement Involving the Endothelin 3 Locus Causes Dermal Hyperpigmentation in the Chicken. PLoS Genetics. 2011. 7(12): e1002412.

Nicole M Le Douarin, Elisabeth Dupin. Multipotentiality of the neural crest. Current Opinion in Genetics & Development.  2003. 13:529–536.

Ben Dorshorst, Ron Okimoto, Chris Ashwell. Genomic Regions Associated with Dermal Hyperpigmentation, Polydactyly and Other Morphological Traits in the Silkie Chicken. Journal of Heredity. 2010. 101(3):339–350.

Cloris D. Faraco, Sonia A.S. Vaz, Maria Veronica D. Pastor, Carol A. Erickson. Hyperpigmentation in the Silkie Fowl Correlates With Abnormal Migration of Fate-Restricted Melanoblasts and Loss of Environmental Barrier Molecules. Developmental Dynamics. 2001. 220:212–225.

Leave a Reply