About this Research Topic
The Wilms’ tumour 1 (WT1) gene was first investigated in 1990 due to its disease link with Wilms’ tumour (a paediatric kidney cancer). Thirty-years on, WT1 has taken us through a journey of many wonders and surprises. Loss-of-function approaches have proven to be powerful in revealing new functions of this gene. Conventional Wt1-KO mice are embryonic lethal, with defects in heart, kidney, gonads, and spleen. Mutations or haploinsufficiency of WT1 in human lead to leukaemia, Denys–Drash, Frasier and WAGR syndromes. As we study Wt1 with immense interest in order to understand disease, study of WT1 expressing progenitor cells has enabled elucidation of the origins of various cell types including heart vasculature, visceral adipocytes and fibrotic liver cells. Wt1 is a gene with precise spatial and temporal expression during development that can be reactivated during tissue repair. Disruption of the gene whether in utero or the adult has catastrophic consequences. WT1 controls key cellular switches including EMT and the reverse process MET. Its multiple isoforms, ability to act as a transcription activator or repressor, and the important post-transcriptional activities all add to the complexity and charm of this gene.
Despite the advances that have been made over the past three decades, we are still at the crossroads with many unanswered questions about Wt1 biology. We are aware that the exact function of Wt1 is cell type- and developmental stage-specific, likely due to the different cellular components that are available. However, we do not always know the exact molecular pathways or cofactors that Wt1 interacts with in a context-specific manner. Comparing with downstream molecular mechanisms, we know relatively little about upstream regulations of Wt1. As shown by many scholarly studies performed by our colleagues, the importance of Wt1 during embryonic development and adult tissue homeostasis is evident. On the other hand, sophisticated investigations of the role of Wt1 in tissue repair and regeneration also give us a glimpse of exciting possibilities about its future in therapeutic interventions. Furthermore, we believe that there are also advances to be made by carefully reflecting on the knowledge that we have gathered about Wt1’s role in regulating developmental processes, and use that to help us unlock our understanding about its role in tissue regeneration. Answering these questions need coordinated efforts of people from different fields.
With this Research Topic, we aim to create a collection of articles to expand the understanding of WT1 by focusing on novel functions, regulation of this gene and its implication in human diseases. We welcome Original Research, General Commentary and Review articles that cover the following sub-topics:
• Cellular and molecular characterization of novel function of WT1 during development and disease
• Regulation of WT1 expression
• WT1 function in development related with human diseases
• WT1 in tissue homeostasis, repair and regeneration
• New tools to study WT1 biology
Keywords: Wt1, disease, development, repair and regeneration, regulation of gene expression, progenitor cells
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