Understanding the Molecular Mechanisms of Renal Progenitor Patterning During Zebrafish Nephrogenesis

The molecular mechanisms underlying nephron patterning establishment are intriguing. The zebrafish embryonic pronephros serves as a simplified and conserved genetic model to study this nephrogenesis process. The zebrafish pronephros arises from renal progenitors that are segmented into distinct epithelial regions including proximal and distal tubule domains, which consist of transporting epithelial cells and intercalated multiciliated cells (MCCs). Using whole mount in situ hybridization, my project uncovered essential roles of the transcription factors mecom and tbx2a/b in patterning of the renal progenitors during zebrafish nephrogenesis. Apart from their functions in segment formation, mecom coordinates with Notch signaling to regulate MCC differentiation, while tbx2b acts downstream of Notch signaling to mediate development of an associated endocrine organ, the corpuscle of Stannius. Meanwhile, I have also discovered Notch signaling as a conserved factor in both zebrafish and mammalian nephron patterning that promotes proximal fates and restricts distal domains. Taken together, my work has identified crucial renal progenitor patterning factors, and has revealed novel molecular mechanisms guiding pronephros development in the zebrafish.