TWIST1 Modulates Cilia Length, Endocytic Vesicle Dynamics, and Cell-Cell Junctions during Neural Tube Morphogenesis
Year: 2025
Type: preprint
Abstract: Background Endocytosis constitutes a fundamental cellular process governing development through coordinated regulation of plasma membrane remodeling and ciliogenesis, processes essential for cell shape changes and embryonic development. Although Twist1 null embryos display complete cranial neural tube closure defects and conditional knockout in neuroectoderm disrupts cranial neural crest cell fate determination and delamination, the function of TWIST1 in neural tube morphogenesis remains unknown. We investigated the basis underlying neuroectodermal morphological abnormalities in TWIST1 mutant embryos, specifically the formation of ectopic lateral bending points and cellular disorganization, by examining TWIST1 function in cilia formation, adherens junction integrity, and endocytic vesicle dynamics. Results Immunofluorescence analysis revealed that cytosolic TWIST1 colocalizes with β-catenin and endocytic regulators LRP2 and RAB11B along the apical surface of cranial neuroectoderm. Twist1 knockout resulted in reduced ciliary length and number. Quantitative PCR and Western blot analyses demonstrated upregulation of RAB11B and β-catenin at mRNA and protein levels in Twist1 mutants. This molecular dysregulation coincided with increased accumulation of apical endocytic vesicles and altered expression profiles of endocytic component genes, ultimately modifying the apical neuroectodermal cell-cell junctions. Conclusion Our findings establish TWIST1 as a regulator of neuroectodermal morphology, demonstrating its ability to modulate ciliogenesis, endocytic vesicle dynamics, and cell-cell integrity.
Authors: Derrick Thomas, Brittany M. Hufft-Martinez, Zarna Lalwani, Vi Pham, Mary Elmeniawi, An J. Tran, Jianming Xi, Irfan Saadi, Walid D. Fakhouri
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Investigating the protective effect of maternal Thm1 heterozygosity against cleft palate, In utero rescue of cleft palate using maternal administration of folic acid, G5537546507, Spinning-Disk Confocal Microscope for Wide-Field, Super-Resolution, and Live-Cell Imaging, G7076593731, G7520202064, The primary role of low NCOA6 expression in the prostate cancer disparity among African American men, Role of SPECC1L cytoskeletal protein in palate elevation dynamics, NRSA Training Core
OpenAlex ID: W4414809250