PT  - JOURNAL ARTICLE
AU  - Jessica W. Bertol
AU  - Shelby Johnston
AU  - Rabia Ahmed
AU  - Victoria K. Xie
AU  - Kelsea M. Hubka
AU  - Lissette Cruz
AU  - Larissa Nitschke
AU  - Marta Stetsiv
AU  - Jeremy P. Goering
AU  - Paul Nistor
AU  - Sally Lowell
AU  - Hanne Hoskens
AU  - Peter Claes
AU  - Seth M. Weinberg
AU  - Irfan Saadi
AU  - Mary C. Farach-Carson
AU  - Walid D. Fakhouri
TI  - TWIST1 interacts with adherens junction proteins during neural tube development and regulates fate transition in cranial neural crest cells
AID  - 10.1101/2021.08.22.457283
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.22.457283
4099  - http://biorxiv.org/content/early/2021/08/22/2021.08.22.457283.short
4100  - http://biorxiv.org/content/early/2021/08/22/2021.08.22.457283.full
AB  - 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 fold 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 interacts with α/β/γ-CATENINS during neural tube closure, and Irf6 is involved in the structural integrity of the neural tube. 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 Twist1 and Irf6 in the neural tube and CNCCs and provides new target genes of Twist1 involved in cytoskeletal remodeling. Furthermore, the association between DNA variations within TWIST1 putative enhancers and human facial morphology is also investigated.SUMMARY STATEMENT This study uncovers a new function of Twist1 in neural tube development and epithelial-to-mesenchymal transition in cranial neural crest cells. Data further shows that Twist1-interacting Irf6 is involved in regulating neural tube integrity.Competing Interest StatementThe authors have declared no competing interest.