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We have been devoting ourselves to fish ion regulation and osmoregulation mechanisms since 1984. We are particularly interested in studying the molecular/cellular mechanisms of how fish operate ionic and acid-base regulation for their body fluid homeostasis, and how these mechanisms are modulated through endocrine systems to cope with a changing environment. In recent years, we have adopted zebrafish as experimental models in serial studies by a variety of molecular physiological and functional genomics approaches, and thus provided new insights into the current knowledge of the related fields by establishing new models of fish ion regulation and opening new windows for the future developments of the related issues.
























1. Zebrafish new model for fish ion regulatory mechanisms  
The current models of ion regulation in fish gill ionocytes were proposed mainly based on the studies in traditional model species (salmon, tilapia, and eel, etc), but the mechanisms are still being debated because of the lack of specific probes or molecular physiological approaches in those previous studies. Taking the advantages of zebrafish in genetic database and molecular physiological approaches, we proposed a new model of ion regulatory mechanisms in fish based on my recent serial studies. In this new model, there are at least three subtypes of ionocytes (NaR cells, HR cells, and NCC-expressing cells) in zebrafish gill/skin, and the 3 types of ionocytes respectively achieve Ca2+ uptake, Na+ uptake/H+ secretion/NH4+ excretion and Cl- uptake through the operations of different sets of ion transporters and enzymes. This model is instrumental in re-shaping our understanding of one of the most fundamental of fish gill ionic regulation mechanisms: subtypes of ionocytes expressing different sets of ion transporters and performing respective transport functions. This also provides a more competent and efficiency platform for future research on the related issues.


2. Proliferation, differentiation and functional regulation of ionocytes in zebrafish

Effects of environmental factors and hormones on cell renewal and proliferation of fish gill ionocytes have been another important issue in fish osmoregulation for a long time, but nothing was known about the molecular mechanisms behind the differentiations of ionocytes and their subtypes until our recent pioneering studies on zebrafish. In zebrafish embryos, several transcription factor (foxi3a/3b and gcm2) were identified as forming a positive regulatory and interacted loop for specification and differentiation of epidermal ionocyte. Based on these results, the 1st model for the molecular pathways of cell differentiation of fish skin/gill ionocytes was proposed, and this opened up a new window to further explore molecular and cellular mechanisms of the functional regulation of ionocytes and the neuroendocrine control.




3. Hormone control of ion regulation in zebrafish

The neuroendocrine systems play a critical role in controlling these molecular/cellular events during acclimation, and many endocrines have been proposed to be involved; however, the molecular physiological mechanisms behind these control pathways are largely unexplored. Zebrafish appears to be an alternative and more powerful model to explore the relevant issues by precisely studying the downstream targets (i.e., ion transporters or ionocytes) and the control pathways of hormone(s). We are focusing our research on the hormones that may control the two best studied transport mechanisms, Ca2+ uptake and Na+ uptake/acid secretion. We are further investigating how different hormones interact and control the ionic and acid-base regulation mechanisms and also test the hypothesis if those control pathways are mediated by the regulation of proliferation and/or differentiation of ionocytes.





4. Climate change and the physiological basis of CO2 and thermal tolerance in marine vertebrates and invertebrates

Using the expertise of our laboratory in studying the acid-base and thermal regulatory processes in teleosts, we expand our research field to other marine species. In close collaboration with other working groups (Dr. Yung-Che Tseng, Dr. Sam Dupont, Dr. Yi-Hsien Su and Dr. Jr-Kai Yu) special emphasis is dedicated to better understand the effects of global warming and ocean acidification on marine species, including cephalopods (squid), echinoderms (sea urchin, sea cucumbers), chordates (Amphioxus) and fish. Using this comparative approach we try to identify unifying physiological principles that marine organisms apply to regulate their internal pH homeostasis. Besides important information regarding the ability to cope with a changing marine environment, these studies will offer important insights regarding common mechanisms of acid-base regulation in marine invertebrate species. This research is still underrepresented in the literature and may represent an important direction to better understand the evolutionary mechanisms of acid-base and ion regulation in animals.