No abstract

Pigment patterns in the integument have long-attracted attention from both scientists and nonscientists alike since their natural attractiveness combines with their excellence as models for the general problem of pattern formation. Pigment cells are formed from the neural crest and must migrate to reach their final locations. In this review, we focus on our current understanding of mechanisms underlying the control of pigment cell migration and patterning in diverse vertebrates. The model systems discussed here -chick, mouse, and zebrafish -each provide unique insights into the major morphogenetic events driving pigment pattern formation. In birds and mammals, melanoblasts must be specified before they can migrate on the dorsolateral pathway. Transmembrane receptors involved in guiding them onto this route include EphB2 and Ednrb2 in chick, and Kit in mouse. Terminal migration depends, in part, upon extracellular matrix reorganization by ADAMTS20. Invasion of the ectoderm, especially into the feather germ and hair follicles, requires specific signals that are beginning to be characterized. We summarize our current understanding of the mechanisms regulating melanoblast number and organization in the epidermis. We note the apparent differences in pigment pattern formation in poikilothermic vertebrates when compared with birds and mammals. With more pigment cell types, migration pathways are more complex and largely unexplored; nevertheless, a role for Kit signaling in melanophore migration is clear and indicates that at least some patterning mechanisms may be highly conserved. We summarize the multiple factors thought to contribute to zebrafish embryonic pigment pattern formation, highlighting a recent study identifying Sdf1a as one factor crucial for regulation of melanophore positioning. Finally, we discuss the mechanisms generating a second, metamorphic pigment pattern in adult fish, emphasizing recent studies strengthening the evidence that undifferentiated progenitor cells play a major role in generating adult pigment cells.

Epithelial layers in developing embryos are known to drive ion currents through themselves that will, in turn, generate small electric fields within the embryo . We hypothesized that the movement of migratory embryonic cells might be guided by such fields, and report here that embryonic quail somite fibroblast motility can be strongly influenced by small DC electric fields . These cells responded to such fields in three ways: (a) The cells migrated towards the cathodal end of the field by extending lamellipodia in that direction . The threshold field strength for this galvanotaxis was between 1 and 10 mV/mm when the cells were cultured in plasma. (b) The cells oriented their long axes perpendicular to the field lines. The threshold field strength for this response for a 90-min interval in the field was 150 mV/mm in F12 medium and between 50 and 100 mV/mm in plasma. (c) The cells elongated under the influence of field strengths of 400 mV/mm and greater . These fibroblasts were therefore able to detect a voltage gradient at least as low as 0.2 mV across their width. Electric fields of at least 10-fold larger in magnitude than this threshold field have been detected in vivo in at least one vertebrate thus far, so we believe that these field effects encompass a physiological range .

SummaryMelanocytes differentiate from the neural crest (NC), which is a transient population of cells that delaminates from the neural tube and migrates extensively throughout the embryo during vertebrate development. Melanoblast specification from NC precursors is a progressive process during which initially pluripotent cells become restricted to the melanogenic lineage and adopt the gene expression profile and morphology of melanocytes. This specification process is governed primarily by Wnt and BMP signaling molecules, although other signaling pathways, such as those activated by Kit and Endothelin 3, can also stimulate melanogenesis. The transcriptional repressor FoxD3 occupies a central role in melanocyte fate determination by repressing melanogenesis in premigratory NC cells and in other NC lineages.

Recent studies show that specification of some neural crest lineages occurs prior to or at the time of migration from the neural tube. We investigated what signaling events establish the melanocyte lineage, which has been shown to migrate from the trunk neural tube after the neuronal and glial lineages. Using in situ hybridization, we find that, although Wnts are expressed in the dorsal neural tube throughout the time when neural crest cells are migrating, the Wnt inhibitor cfrzb-1 is expressed in the neuronal and glial precursors and not in melanoblasts. This expression pattern suggests that Wnt signaling may be involved in specifying the melanocyte lineage. We further report that Wnt-3a-conditioned medium dramatically increases the number of pigment cells in quail neural crest cultures while decreasing the number of neurons and glial cells, without affecting proliferation. Conversely, BMP-4 is expressed in the dorsal neural tube throughout the time when neural crest cells are migrating, but is decreased coincident with the timing of melanoblast migration. This expression pattern suggests that BMP signaling may be involved in neural and glial cell differentiation or repression of melanogenesis. Purified BMP-4 reduces the number of pigment cells in culture while increasing the number of neurons and glial cells, also without affecting proliferation. Our data suggest that Wnt signaling specifies melanocytes at the expense of the neuronal and glial lineages, and further, that Wnt and BMP signaling have antagonistic functions in the specification of the trunk neural crest.