Evidence That MIF Plays a Role in the Development of Pigmentation Patterns in the Frog

Abstract

A ventrally localized melanization-inhibiting factor (MIF) may play an important role in the expression of dorsal-ventral pigment patterns of amphibians. In efforts to purify this putative MIF, ventral skin conditioned medium (VCM) from Rana forreri was partially fractionated and used to immunize mice. A monoclonal antibody that has the ability to block the activity of MIF was isolated, and an immunoaffinity matrix was prepared by cross-linking the antibody to protein G-Sepharose. The fraction of VCM that bound to the affinity matrix decreased the number of melanized cells in the Xenopus laevis neural tube explant assay, but did not reduce significantly the number of cells that emigrated. The monoclonal antibody was used for immunohistochemical studies on R. pipiens skin. Strong staining with the antibody was observed beneath the basement membrane, in mucous glands, and in the subcutaneous tissue of the ventral skin. A weak staining was also observed in the ground substances of both ventral and dorsal skin. These results confirm that a monoclonal antibody has been secured against at least one of the MIF constituents and that it is useful as a probe in detecting the distribution of MIF in tissues. The results of its use in this study support the hypothesis that MIF plays a role in the expression, development, and maintenance of the dorsal-ventral pigmentation patterns of frogs.

Not just black and white: Pigment pattern development and evolution in vertebrates

“…In amphibians, a ventral specific factor, melanization inhibiting factor (MIF), represses differentiation and melanization of melanocytes in vitro [76,77]. MIF is highly expressed in unmelanized ventral skin and not only suppresses melanization, but also appears to promote iridophore localization in this region [78,79]. Similar to MIF, an agouti homolog expressed mainly in the golfish ventrum blocks melanization in cell culture [80].…”

Origin of adult‐type pigment cells forming the asymmetric pigment pattern, in Japanese flounder (Paralichthys olivaceus)

“…Among vertebrates, the most common skin pigment pattern is the dorsoventral pattern in which the dorsal surface is darkly colored, and the ventral surface is pale (Ohsugi and Ide, 1983;Fukuzawa et al, 1995;Candille et al, 2004). Generally, this pigment pattern has a bilateral symmetry.…”

Insights Into Pigmentary Phenomena Provided by Grafting and Chimera Formation in the Axolotl

“…Among the more important questions about the development and expression of pigmentation patterns are those that concern the point or points in time when chromatoblasts (pro-pigment cells) are committed to specific pathways of differentiation; or, in other words, when chromatoblasts are determined in the embryonic sense. As has been frequently discussed (see Bagnara, 1987;Erickson, 1993;Frost-Mason et al, 1994;Fukuzawa et al, 1995), there is evidence that some chromatoblasts are at least partially determined at the level of the crest before emigration, that determination may occur en route, or that determination occurs after migration due to the action of factors present in the skin or other organs populated by neural crest cells. The importance of the latter concept in the development and expression of integumental pigmentation patterns is a view championed by Bagnara and colleagues (1979).…”

“…In this view, the neural crest is considered to be a source of stem cells that are not committed to a specific pathway of pigment cell differentiation until late in their emigration from the crest; or, more likely, until after their arrival in specific areas of the skin where they are exposed to local integumental factors that influence their differentiation. One such factor, melanization inhibiting factor (MIF), was suggested to be important in the establishment of dorsal-ventral patterns in amphibians (Fukuzawa and Ide, 1988;Fukuzawa and Bagnara, 1989;Fukuzawa et al, 1995). Similarly, a melanization-stimulating factor (MSF) was also suggested to be important in the expression of frog pigmentation patterns (Mangano et al, 1992).…”

“…One such factor could be the "inhibitor" that Thibaudeau and F'rost-Mason (1992) suggested was produced by white skin of the axolotl. It is possible that other such hypothetical elements are related to the putative factors MIF (Bagnara and Fukuzawa, 1990;Fukuzawa and Ide, 1988;Fukuzawa and Bagnara, 1989;Fukuzawa et al, 1995) and MSF Mangano et al, 1992;Zuasti et al, 1992;Zuasti et al, 1993). Such factors have been postulated to play a role in the normal and abnormal pigmentation patterns of all vertebrates, from lower fishes to man .…”