TWIST1 interacts with β/δ-catenins during neural tube development and regulates fate transition in cranial neural crest cells

Abstract

Cell fate determination is a necessary and tightly regulated process for producing different cell types and structures during development. Cranial neural crest cells (CNCCs) are unique to vertebrate embryos and emerge from the neural plate borders into multiple cell lineages that differentiate into bone, cartilage, neurons, and glial cells. We previously reported that Irf6 genetically interacts with Twist1 during CNCC-derived tissue formation. Here, we investigated the mechanistic role of Twist1 and Irf6 at early stages of craniofacial development. Our data indicates that TWIST1 is expressed in endocytic vesicles at the apical surface and interacts with β/δ-CATENINS during neural tube closure, and Irf6 is involved in defining neural fold borders by restricting AP2α expression. Twist1 suppresses Irf6 and other epithelial genes in CNCCs during epithelial-to-mesenchymal transition (EMT) process and cell migration. Conversely, a loss of Twist1 leads to a sustained expression of epithelial and cell adhesion markers in migratory CNCCs. Disruption of TWIST1 phosphorylation in vivo leads to epidermal blebbing, edema, neural tube defects, and CNCC-derived structural abnormalities. Altogether, this study describes an uncharacterized function of mammalian Twist1 and Irf6 in the neural tube and CNCCs and provides new target genes of Twist1 involved in cytoskeletal remodeling. DNA variations within TWIST1 putative enhancers are significantly associated with human facial morphology in a large European cohort.

A novel IRF6 gene mutation impacting the regulation of TGFβ2-AS1 in the TGFβ pathway: A mechanism in the development of Van der Woude syndrome

“…Through pathways involving TGFβ3 and TWIST1, IRF6 influences the behavior of cranial neural crest cells, affecting the development of key tissues like the palate. This underscores IRF6’s significant role in cellular differentiation, migration, and overall craniofacial embryonic development, orchestrating the sophisticated processes of facial formation and organogenesis ( Ke et al, 2015 ; Bertol et al, 2022 ). Based on the results from immunofluorescence localization, we deduced that the novel mutant IRF6 had a reduced ability to enter the cell nucleus.…”

The Unknown Epithelial and Mesenchymal States Cannot Support Epithelial-Mesenchymal Transition as a Meaningful Concept

“…Similar expression patterns of Zeb1 and Zeb2 are also present during mouse embryonic development (Vandewalle et al, 2009). TWIST1 and its orthologues are involved in regulation of gastrulation and body axis patterning of Drosophila embryos (Simpson, 1983), pluripotency and differentiation of embryonic stem cells (Fan et al, 2020), mesoderm differentiation, differentiation of embryonic hematopoietic stem/progenitor cells (Kulkeaw et al, 2017), and particularly, cell fate decision of neural crest and development of neural crest derived structures (Bertol et al, 2022;Fan et al, 2021; O'Rourke and Tam, 2002;Soldatov et al, 2019). Snai1 and Snai2 were intensely studied in the specification and migration of neural crest in vertebrates (Aybar et al, 2003;LaBonne and Bronner-Fraser, 2000;Nieto et al, 1994;Tríbulo et al, 2004).…”

Epithelial-Mesenchymal Transition: A Groundless Skyscraper

“…Similar expression patterns of Zeb1 and Zeb2 are also present during mouse embryonic development (Vandewalle et al, 2009). TWIST1 and its orthologues are involved in regulation of gastrulation and body axis patterning of Drosophila embryos (Simpson, 1983), pluripotency and differentiation of embryonic stem cells (Fan et al, 2020), mesoderm differentiation, differentiation of embryonic hematopoietic stem/progenitor cells (Kulkeaw et al, 2017), and particularly, cell fate decision of neural crest and development of neural crest derived structures (Bertol et al, 2022;Fan et al, 2021;OʹRourke and Tam, 2002;Soldatov et al, 2019). Snai1 and Snai2 were intensely studied in the specification and migration of neural crest in vertebrates (Aybar et al, 2003;LaBonne and Bronner-Fraser, 2000;Nieto et al, 1994;Tríbulo et al, 2004).…”