Functional Divergence and Redundant Functions of the Hippo Pathway Effectors YAP and TAZ in Nephrogenesis
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posted on 2024-07-25, 03:05authored byCaroline Monserrat Lara
In this dissertation, I will provide insight into the role of the downstream effectors of the Hippo pathway, Yes-associated protein 1 (YAP), and paralog WW domain- containing transcription regulator 1 (TAZ (wwtr1)) in renal organogenesis and provide the foundation for further research into the molecular mechanisms underlying kidney development and associated pathologies. The kidney, a complex organ crucial for maintaining homeostasis, undergoes intricate developmental processes to form functional nephron units. Understanding the mechanisms behind kidney development is paramount for elucidating the etiology of renal congenital disabilities and acquired diseases. The Hippo pathway is known for its involvement in various cellular functions, including cell fate determination and differentiation, and emerges as a critical player in renal organogenesis. The downstream effectors of the Hippo pathway, YAP, and TAZ (wwtr1), possess highly conserved protein sequences, leading to the assumption of functional redundancy in their roles during pronephros ontogeny. However, through systematic loss of function studies in the zebrafish Danio rerio, we have uncovered the distinct roles of yap and taz(wwtr1) in developing the different nephron segments. Our findings suggest that (i) there is divergence in the functions of yap and taz(wwtr1) during nephrogenesis and that (ii) both yap and taz(wwtr1) are essential for directing proper ontogeny of multiciliated cells within the nephron. These insights shed new light on the intricate roles of Hippo signaling pathways in renal organogenesis and the specialized cell populations in the nephron.