A Positive Regulatory Loop between foxi3a and foxi3b Is Essential for Specification and Differentiation of Zebrafish Epidermal Ionocytes 英文参考文献.docVIP

APositiveRegulatoryLoopbetweenfoxi3aandfoxi3bIs EssentialforSpecificationandDifferentiationof ZebrafishEpidermalIonocytes Chung-DerHsiao1,2,May-SuYou2,Ying-JeyGuh1,3,MingMa2,Yun-JinJiang2*,Pung-PungHwang1* 1Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan, 2Institute of Molecular and Cell Biology, Singapore, Singapore, 3GraduateInstituteofLifeSciences,NationalDefenseMedicalCenter,Taipei,Taiwan 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. Methodology/Principal Findings. In zebrafish, we demonstrated that Delta-Notch-mediated lateralinhibition plays a vital role in singling out epidermal ionocyte progenitors fromepidermalstemcells.Theentireepidermalionocytedomainofgeneticmutantsandmorphants,whichfailedtotransmit the DeltaC-Notch1a/Notch3 signal from sending cells (epidermal ionocytes) to receiving cells (epidermal stem cells), differentiatesintoepidermalionocytes.ThelowNotchactivityinepidermalionocyteprogenitorsispermissiveforactivating wingedhelix/forkheadboxtranscriptionfactorsoffoxi3aandfoxi3b.Throughgain-andloss-of-functionassays,weshowthat 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/Significance. This study provides a framework to show the molecular mechanismcontrollingepidermalionocytespecificationanddifferentiationinalowvertebrateforthefirsttime.Wepropose thatthepositiveregulatoryloopbetweenfoxi3aandfoxi3bnotonlydrivesearlyionocytedifferentiationbutalsopreventsthe completeblockageofionocytedifferentiationwhenthemasterregulator