A positive regulatory loop between foxi3a and foxi3b is essential for specification and differentiation of zebrafish epidermal ionocytes.
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.
Hsiao
Chung-Der
CD
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
You
May-Su
MS
Guh
Ying-Jey
YJ
Ma
Ming
M
Jiang
Yun-Jin
YJ
Hwang
Pung-Pung
PP
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
D007477:Ions; D001119:Arginase; D006180:Proton-Translocating ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium