Evolutionary diversification of the canonical Wnt signaling effector TCF/LEF in chordates

Abstract

Wnt signaling is essential during animal development and regeneration, but also plays an important role in diseases such as cancer and diabetes. The canonical Wnt signaling pathway is one of the most conserved signaling cascades in the animal kingdom, with the T‐cell factor/lymphoid enhancer factor (TCF/LEF) proteins being the major mediators of Wnt/β‐catenin‐regulated gene expression. In comparison with invertebrates, vertebrates possess a high diversity of TCF/LEF family genes, implicating this as a possible key change to Wnt signaling at the evolutionary origin of vertebrates. However, the precise nature of this diversification is only poorly understood. The aim of this study is to clarify orthology, paralogy, and isoform relationships within the TCF/LEF gene family within chordates via in silico comparative study of TCF/LEF gene structure, molecular phylogeny, and gene synteny. Our results support the notion that the four TCF/LEF paralog subfamilies in jawed vertebrates (gnathostomes) evolved via the two rounds of whole‐genome duplications that occurred during early vertebrate evolution. Importantly, gene structure comparisons and synteny analysis of jawless vertebrate (cyclostome) TCFs suggest that a TCF7L2‐like form of gene structure is a close proxy for the ancestral vertebrate structure. In conclusion, we propose a detailed evolutionary path based on a new pre‐whole‐genome duplication vertebrate TCF gene model. This ancestor gene model highlights the chordate and vertebrate innovations of TCF/LEF gene structure, providing the foundation for understanding the role of Wnt/β‐catenin signaling in vertebrate evolution.

The Role of Vti1a in Biological Functions and Its Possible Role in Nervous System Disorders

“…Surprisingly, the VTI1A-TCF7L2 gene fusion transcripts were detected in the tumor tissue and plasma of GBM ( Wang et al, 2020 ). The TCF7L2 gene product is a transcription factor containing a high mobility group cassette that plays an essential role in the Wnt signaling pathway ( Su et al, 2015 ; Torres-Aguila et al, 2022 ). The Wnt signaling pathway has been shown to play an important role in the progression of glioma by affecting the differentiation, proliferation, migration, and apoptosis of neural cells ( Tompa et al, 2019 ; Pei et al, 2022 ).…”

Marine genomics, transcriptomics, and beyond in developmental, cell, and evolutionary biology

“…Based on these, they showed novel aspects of development in O. dioca , such as mitotic cell arrest and left–right asymmetry. Torres‐Aguila et al (2022) focused on the contribution of the Wnt signaling components in chordate evolution, and analyzed the gene structure of TCF/LEF genes. By using TCF/LEF genes from marine invertebrates as outgroups, they were able to predict the ancestral gene structure of TCF/LEF in vertebrates, which is now observed in the TCF7L2‐ like gene of the lamprey.…”