Effect of Embryonic Alcohol Exposure on Craniofacial and Skin Melanocyte Development: Insights from Zebrafish (Danio rerio)

Abstract

Alcohol is a common addictive substance and prenatal alcohol exposure could cause fetal alcohol spectrum disorder (FASD) and can lead to various birth defects. The small teleost zebrafish (Danio rerio) has been identified as a fine animal model in developmental biology and toxicological research. Zebrafish models are widely used to study the harmful effects of alcohol and limited studies are available on the craniofacial and skin malformations associated with FASD. The present study attempts to investigate the effect of alcohol on early zebrafish embryonic development. The effects of prenatal alcohol exposure on neural crest cell-derived organ formation, including pharyngeal dentition, palatal bones and skin melanocytes were analysed. Whole-mount cartilage and bone staining and imaging techniques were applied to determine the effects of alcohol on the above-mentioned structures. The tooth size and shape were affected by alcohol exposure, but the number of teeth in the pharyngeal dentition was not affected. Only first-generation teeth showed size differences. The alcohol-exposed ethmoid bone, which is homologous to the human hard palate, was smaller and less dense in cell arrangement compared with the control medial ethmoid bone. The skin pigmentation defects included reduced melanocyte density, melanin contraction, smaller melanocyte surface area and aberrations in melanosome dispersion, revealing that alcohol significantly influenced and downregulated each and every step of the melanocyte developmental process. This descriptive study summarises the effects of alcohol on the development of neural crest cell-derived structures and highlights the importance of zebrafish in studying the phenotypic characteristics of fetal alcohol spectrum disorder.

Characterising the Effect of Wnt/β-Catenin Signalling on Melanocyte Development and Patterning: Insights from Zebrafish (Danio rerio)

“…The effect of early embryonic exposure to small molecules of Wnt regulatory chemicals on melanocyte formation, phenotypic development, migration, and patterning has not been observed in any studies using any animal model, including zebrafish [ 40 , 41 , 42 ]. Exclusively, this is the first study to investigate the effect of early embryonic Wnt signalling activity on zebrafish melanocyte development and patterning.…”

Ethanol Metabolism and Melanoma

“…Ethanol exposure may disrupt a range of melanocyte development processes leading to defective skin pigmentation [130], in which the role of ethanol metabolism is unknown. On the other hand, as previously mentioned in Section 3.1, ethanol increases cAMP/PKA pathway activity, which has been implicated in melanocyte pigmentation, melanomagenesis [131,132], and therapy resistance [133].…”