COUP-TFI specifies the medial entorhinal cortex identity and induces differential cell adhesion to determine the integrity of its boundary with neocortex｜中央研究院 細胞與個體生物學研究所

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How vertebrates evolved different traits for acid excretion to maintain body fluid pH homeostasis is largely unknown. We report the evolution of Na+/H+ exchanger (NHE)-mediated NH4+ excretion in fishes, and the coevolution with increased ammoniagenesis and accompanying gluconeogenesis is speculated to benefit vertebrates in terms of both internal homeostasis and energy metabolism response to acidic stress. The findings provide new insights into our understanding of the possible adaptation of fishes to progressing global environmental acidification. In human kidney, titratable H+ and NH4+ comprise the two main components of net acid excretion. H+-ATPase-mediated H+ excretion may have developed in stenohaline lampreys when they initially invaded freshwater from marine habitats, but this trait was lost in most fishes. Instead, increased reliance on NHE-mediated NH4+ excretion was gradually developed and intensified during fish evolution. Further investigations on more species will be needed to support our hypothesis.