Inhibition of Wnt/β‐catenin Signaling Pathway on Melanogenesis‐ Insights from Zebrafish (Danio rerio)

Abstract

IntroductionVertebrate color patterns are composed of specialized pigment‐producing cells, the chromatophores. Melanin is the main pigment type that colors the skin and skin appendages in mammals. Melanin is produced by specialized cells called melanocytes. Melanocytes have embryonic neural crest cells origin and their development and functions are ubiquitous across vertebrates, residing in dermal and epidermal skin layers. Studies of melanogenesis have provided experimentalists with a valuable system for understanding pattern formation in the developing embryo. In addition, studying these mechanisms may have important consequences for the clinical sciences. Alcohol is a widely abused teratogenic substance. Fetal alcohol spectrum disorder (FASD) is described as birth defects associated with prenatal alcohol exposure (PAE). PAE is likely one of the leading causes of birth defects but pathophysiology of FASD associated body pigmentation disorders are needed to be investigated further. Zebrafish (Danio rerio) (ZF) is identified as a good model to study FASD and melanocyte biology. Wnt signaling pathway is a conserved signal transduction pathway which is important in embryonic development and it regulates many aspects of melanogenesis. The current study was designed to investigate the effect of Alcohol‐Wnt signaling pathway activity on ZF melanogenesis.Materials and MethodsWild‐type (WT) ZF embryos were treated with Wnt pathway inhibitor (LiCl) and combined chemical treatment (LiCl and 1% alcohol) at 10 hours post fertilization (hpf). The differential effects of above substances on early development, differentiation, patterning of melanocytes were investigated using cell biology and imaging techniques.ResultsMelanocytes of LiCl exposed samples showed defects in migration, arrangement and survival. Ectopic melanocytes and developmental aberrations of eye pigmentation were noticed in both chemical treatments. Significant variation of the melanocyte cell size, shape and body pigmentation patterning was observed among the LiCl and combined treated samples compared to the control.ConclusionEmbryonic LiCl and alcohol exposures affect the development and patterning of the melanocytes in ZF. The molecular mechanisms underlying the above phenotypes will be investigated further to understand the FASD associated pigmentation defects.