title: A positive regulatory loop between foxi3a and foxi3b is essential for specification and differentiation of zebrafish epidermal ionocytes.
abstract: BACKGROUND
  Epidermal ionocytes play essential roles in the transepithelial transportation of ions, water, and acid-base balance in fish embryos before their branchial counterparts are fully functional. However, the mechanism controlling epidermal ionocyte specification and differentiation remains unknown.
  
  
  RESULTS
  In zebrafish, we demonstrated that Delta-Notch-mediated lateral inhibition plays a vital role in singling out epidermal ionocyte progenitors from epidermal stem cells. The entire epidermal ionocyte domain of genetic mutants and morphants, which failed to transmit the DeltaC-Notch1a/Notch3 signal from sending cells (epidermal ionocytes) to receiving cells (epidermal stem cells), differentiates into epidermal ionocytes. The low Notch activity in epidermal ionocyte progenitors is permissive for activating winged helix/forkhead box transcription factors of foxi3a and foxi3b. Through gain- and loss-of-function assays, we show that the foxi3a-foxi3b regulatory loop functions as a master regulator to mediate a dual role of specifying epidermal ionocyte progenitors as well as of subsequently promoting differentiation of Na(+),K(+)-ATPase-rich cells and H(+)-ATPase-rich cells in a concentration-dependent manner.
  
  
  CONCLUSIONS
  This study provides a framework to show the molecular mechanism controlling epidermal ionocyte specification and differentiation in a low vertebrate for the first time. We propose that the positive regulatory loop between foxi3a and foxi3b not only drives early ionocyte differentiation but also prevents the complete blockage of ionocyte differentiation when the master regulator of foxi3 function is unilaterally compromised.
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors: Chung-Der
authors: CD
authors: Hsiao
authors: May-Su
authors: MS
authors: You
authors: Ying-Jey
authors: YJ
authors: Guh
authors: Ming
authors: M
authors: Ma
authors: Yun-Jin
authors: YJ
authors: Jiang
authors: Pung-Pung
authors: PP
authors: Hwang
mesh_terms: D000136:Acid-Base Equilibrium / Q000235:genetics; D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology; D017403:In Situ Hybridization; D007477:Ions / Q000378:metabolism; D007668:Kidney / Q000502:physiology; D011188:Potassium / Q000502:physiology; D006180:Proton-Translocating ATPases / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D007477:Ions; D001119:Arginase; D006180:Proton-Translocating ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium