| Summary: | The great diversity of color patterns observed among amphibians is largely explained by the differentiation of relatively few pigment cell types during development. Mexican axolotls present a variety of color phenotypes that span the continuum from leucistic to highly melanistic. The <i>melanoid</i> axolotl is a Mendelian variant characterized by large numbers of melanophores, proportionally fewer xanthophores, and no iridophores. Early studies of <i>melanoid</i> were influential in developing the single-origin hypothesis of pigment cell development, wherein it has been proposed that all three pigment cell types derive from a common progenitor cell, with pigment metabolites playing potential roles in directing the development of organelles that define different pigment cell types. Specifically, these studies identified xanthine dehydrogenase (XDH) activity as a mechanism for the permissive differentiation of melanophores at the expense of xanthophores and iridophores. We used bulked segregant RNA-Seq to screen the axolotl genome for <i>melanoid</i> candidate genes and identify the associated locus. Dissimilar frequencies of single-nucleotide polymorphisms were identified between pooled RNA samples of wild-type and <i>melanoid</i> siblings for a region on chromosome 14q. This region contains <i>gephyrin</i> (<i>Gphn</i>), an enzyme that catalyzes the synthesis of the molybdenum cofactor that is required for XDH activity, and <i>leukocyte tyrosine kinase</i> (<i>Ltk</i>), a cell surface signaling receptor that is required for iridophore differentiation in zebrafish. Wild-type <i>Ltk</i> crispants present similar pigment phenotypes to <i>melanoid</i>, strongly implicating <i>Ltk</i> as the <i>melanoid</i> locus. In concert with recent findings in zebrafish, our results support the idea of direct fate specification of pigment cells and, more generally, the single-origin hypothesis of pigment cell development.
|
|---|