The naked cuticle (or naked) gene in Drosophila acts as a negative regulator of wingless signaling. Cloning of the gene revealed that it encodes a protein with an EF hand that may interact with a divalent cation (Zeng, 2000). Expression of naked is induced by wingless, generating a negative feedback loop. The Naked protein can bind to Dishevelled, an interaction that downregulates Dsh activity (Rousset, 2001). There are two human and mouse naked homologs (Wharton, 2001; Yan 2001). Mice with compound mutations in both nkd genes are viable and have subtle cranial bone morphology phenotypes (Zhang, 2007)