The present study using zebrafish as a model explores the role of isotocin, a 
homolog of oxytocin, in controlling ion regulatory mechanisms. Double-deionized 
water treatment for 24 h significantly stimulated isotocin mRNA expression in 
zebrafish embryos. Whole-body Cl(-), Ca(2+), and Na(+) contents, mRNA 
expressions of ion transporters and ionocyte-differentiation related 
transcription factors, and the number of skin ionocytes decreased in isotocin 
morphants. In contrast, overexpression of isotocin caused an increase in 
ionocyte numbers. Isotocin morpholino caused significant suppression of foxi3a 
mRNA expression, while isotocin cRNA stimulated foxi3a mRNA expressions at the 
tail-bud stage of zebrafish embryos. The density of P63 (an epidermal stem cell 
marker)-positive cells was downregulated by isotocin morpholinos and was 
upregulated by isotocin cRNA. Taken together, isotocin stimulates the 
proliferation of epidermal stem cells and differentiation of ionocyte 
progenitors by regulating the P63 and Foxi3a transcription factors, consequently 
enhancing the functional activities of ionocytes.