English

Abstract

expresses a different set of genes. The proper expression of the gene set for a given cell type is regulated and maintained through epigenetic mechanisms1–4. Two epigenetic mechanisms are responsible for the establishment and maintenance of cell properties in higher eukaryotes: DNA methylation and histone modification. Generally, the genetic information encoded within a DNA sequence tends to be static without variation. Even if variations occur as a result of mutations, the consequences are discrete: either the presence or absence of the DNA mutation accompanying certain phenotypes. In contrast, the epigenetic marks obtained through DNA methylation and histone modification are usually malleable in terms of their modification levels. This plastic nature of the epigenetic modifications can be further influenced by environmental factors such as diet, toxic chemicals and stress, which is a previously unrecognised but important issue for human health. Nevertheless, it is largely unknown to what extent the environmental exposure affects the epigenetic modification process. Owing to the recent development of new DNA sequencing technologies, we have gained an unprecedented global overview of epigenetic modifications at the genomic level. However, the biological roles of these epigenetic modifications are not well understood, possibly because the majority of epigenetic studies have focused primarily on cancer and stem cells, and not in a broader context of animal development5. In that regard, neural crest cells (NCCs) are an excellent choice for the following reasons. NCCs play important roles in the developmental process of vertebrates, providing a battery of different cell types. Some unique features of NCCs are their migration capability and maintenance of mulipotency during development, which probably makes them vulnerable to subtle environmental changes. In fact, a large number of human disorders are caused by defects in the development and migration of NCCs, collectively referred to as neurocristopathies. The neurocristopaties are well-known for their low levels of penetrance, suggesting the potential involvement of non-genetic components. These non-genetic components might be of epigenetic origin since epigenetic modifications are known to play significant roles in the establishment and maintenance of stem cells, including NCCs. In this short review, we will discuss possible roles of epigenetic mechanisms and environment in the development of NCCs.