Transcriptional targets of TWIST1 in the cranial mesoderm regulate cell-matrix interactions and mesenchyme maintenance

Autor: Junwen Wang, Vanessa Jones, Melinda Power, Heidi Bildsoe, Xiaochen Fan, Patrick P.L. Tam, David A.F. Loebel, Emilie E. Wilkie, Jing Qin, Ator Ashoti
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
PROTEIN
FGF and mesoderm formation
Madin Darby Canine Kidney Cells
bHLH factor
Mesoderm
Mice
Craniofacial
Cranial mesoderm
Genetics
Mice
Knockout
CRANIOFACIAL MUSCLES
Gene Expression Regulation
Developmental
Nuclear Proteins
Cell Differentiation
TGF-BETA
Cell biology
Extracellular Matrix
DOMAIN RECEPTOR 2
medicine.anatomical_structure
DIFFERENTIATION
Neural Crest
embryonic structures
NEURAL-TUBE
Twist1
PROMOTES TUMOR-METASTASIS
Epithelial-Mesenchymal Transition
animal structures
Mesenchyme
Morphogenesis
Biology
Cell Line
03 medical and health sciences
Dogs
TGF beta signaling pathway
medicine
Paraxial mesoderm
Animals
BREAST-CANCER
Molecular Biology
Binding Sites
BETA-IG-H3 INTERACTS
Skull
Twist-Related Protein 1
Mesenchymal Stem Cells
Cell Biology
030104 developmental biology
Extracellular matrix-cell interaction
MORPHOGENESIS
NODAL
Developmental Biology
TGFBI
Zdroj: Developmental Biology, 418(1), 189-203. ACADEMIC PRESS INC ELSEVIER SCIENCE
ISSN: 0012-1606
DOI: 10.1016/j.ydbio.2016.08.016
Popis: TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. We have previously shown that, in the absence of TWIST1, cells within the cranial mesoderm adopt an abnormal epithelial configuration via a process reminiscent of a mesenchymal to epithelial transition (MET). Here, we show by gene expression analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics. By comparing the transcriptional profiles of cranial mesoderm-specific Twist1 loss-of-function mutant and control mouse embryos, we identified a set of genes that are both TWIST1-dependent and predominantly expressed in the mesoderm. ChIP-seq was used to identify TWIST1-binding sites in an in vitro model of a TWIST1-dependent mesenchymal cell state, and the data were combined with the transcriptome data to identify potential target genes. Three direct transcriptional targets of TWIST1 (Ddr2, Pcolce and Tgfbi) were validated by ChIP-PCR using mouse embryonic tissues and by luciferase assays. Our findings reveal that the mesenchymal properties of the cranial mesoderm are likely to be regulated by a network of TWIST1 targets that influences the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures.
Databáze: OpenAIRE
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