Developmental Genetics of Color Pattern Establishment in Cats
We apply developmental and single cell gene expression analysis to fetal skin of domestic cats, together with genetic characterization of Mendelian color variation, to identify when, where, and how, during fetal development, felid color patterns are established. Prior to the appearance of hair follicle placodes, we identify changes in epidermal thickness that represent a signature of color pattern establishment, and that are preceded by a pre-pattern of gene expression in which the secreted Wnt inhibitor encoded by Dickkopf 4 (Dkk4) plays a central role. We also demonstrate that mutations in Dkk4 underlie the Ticked pattern mutation in cats. Our results bring molecular understanding to how the leopard got its spots, suggest that similar mechanisms underlie periodic color pattern and periodic hair follicle spacing, and provide a genomic framework to explore natural selection for diverse pattern types in wild felids. Overall design: 3 single-cell RNAseq data sets generated from fetal cat skin at different fetal timepoints