During palatal fusion, the midline epithelial seam (MES) degrades to achieve mesenchymal confluence. Epithelial mesenchymal transition (EMT) is one mechanism which is active in MES degradation. TGF-β induces EMT in medial edge epithelium (MEE) by down-regulation of an epithelial marker, E-cadherin. Microtubule disassembly impaired palatal fusion leading to a multi-layered MES in the mid-region. In this study, we investigated the effect of microtubule disruption on the regulation of the E-cadherin/catenin adhesion complex. Nocodazole (NDZ) enhanced the accumulation of the adhesion complex at cell-cell contacts in MEE, while loss of the adhesion complex was observed in the control. NDZ caused aberrant regulation of the E-cadherin transcriptional repressors (Snail and Zeb) and the activator (c-MYC) through inhibition of the TGF-β/SMAD2 signaling pathway, which led to a failure in EMT. These results suggest that the microtubule cytoskeleton plays an important role in mediating TGF-β/SMAD2 signals to control E-cadherin gene expression in MEE during palatal fusion.
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http://dx.doi.org/10.1387/ijdb.120117yk | DOI Listing |
Congenit Anom (Kyoto)
December 2024
Department of Molecular Craniofacial Embryology and Oral Histology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Sonic hedgehog (Shh) is expressed in the oropharyngeal epithelium, including the frontonasal ectodermal zone (FEZ), which is defined as the boundary between Shh and Fgf8 expression domains in the frontonasal epithelium. To investigate the role of SHH signaling from the oropharyngeal epithelium, we generated mice in which Shh expression is specifically deleted in the oropharyngeal epithelium (Isl1-Cre; Shh). In the mutant mouse, Shh expression was excised in the oropharyngeal epithelium as well as FEZ and ventral forebrain, consistent with the expression pattern of Isl1.
View Article and Find Full Text PDFEnviron Toxicol Pharmacol
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Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou450003, Henan, China. Electronic address:
Cleft palate is the most prevalent congenital condition. Cleft palate is brought on by an exogenous chemical called all-trans retinoic acid (atRA). In order to indirectly control gene expression, long chain non-coding RNAs (lncRNAs) act as competitive endogenous RNA (ceRNA) sponges.
View Article and Find Full Text PDFCureus
November 2024
Otolaryngology - Head and Neck Surgery, Freeman Health System, Joplin, USA.
Klippel-Feil syndrome (KFS) is a rare congenital condition characterized by the fusion of cervical vertebrae. It classically presents with a triad of symptoms: limited cervical range of motion, a low posterior hairline, and a short neck. Common otolaryngological manifestations include hearing loss, dysphagia, cleft palate, jaw disorders, thyroid abnormalities, and ear malformations, highlighting the importance of KFS awareness in the field of otolaryngology.
View Article and Find Full Text PDFEur J Hum Genet
December 2024
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Myogenic fusion, primarily regulated by the Myomaker and Myomixer proteins, is essential for skeletal muscle development, yet its mechanisms remain poorly understood. This study presents the clinical and molecular details of the third and fourth reported patients with biallelic variants in MYMX, the gene that encodes Myomixer. We identified a homozygous truncating variant [c.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76, Stockholm, Sweden.
Inversions are balanced structural variants that often remain undetected in genetic diagnostics. We present a female proband with a de novo Chromosome 15 paracentric inversion, disrupting MEIS2 and NUSAP1. The inversion was detected by short-read genome sequencing and confirmed with adaptive long-read sequencing.
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