title: Zeb1 regulates E-cadherin and Epcam (epithelial cell adhesion molecule) expression to control cell behavior in early zebrafish development.
abstract: The ZEB1 transcription factor is best known as an inducer of epithelial-mesenchymal transitions (EMT) in cancer metastasis, acting through transcriptional repression of CDH1 (encoding E-cadherin) and the EMT-suppressing microRNA-200s (miR-200s). Here we analyze roles of the ZEB1 zebrafish orthologs, Zeb1a and Zeb1b, and of miR-200s in control of cell adhesion and morphogenesis during gastrulation and segmentation stages. Loss and gain of function analyses revealed that Zeb1 represses cdh1 expression to fine-tune adhesiveness of migrating deep blastodermal cells. Furthermore, Zeb1 acts as a repressor of epcam in the deep cells of the blastoderm and may contribute to control of epithelial integrity of enveloping layer cells, the outermost cells of the blastoderm. We found a similar ZEB1-dependent repression of EPCAM expression in human pancreatic and breast cancer cell lines, mediated through direct binding of ZEB1 to the EPCAM promoter. Thus, Zeb1 proteins employ several evolutionary conserved mechanisms to regulate cell-cell adhesion during development and cancer.
authors.affiliation: Developmental Biology, Institute Biology I, Faculty of Biology, Albert-Ludwigs-University Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany.
authors.forename: Corinne
authors.initials: C
authors.lastname: Vannier
authors.forename: Kerstin
authors.initials: K
authors.lastname: Mock
authors.forename: Thomas
authors.initials: T
authors.lastname: Brabletz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Driever
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000378:metabolism* / Q000502:physiology*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015820:Cadherins; C579542:Cdh1 protein, zebrafish; C524037:EpCAM protein, zebrafish; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D014157:Transcription Factors; C486307:ZEB1 protein, human; D029961:Zebrafish Proteins; D000071799:Zinc Finger E-box-Binding Homeobox 1; C583292:zeb1b protein, zebrafish
keywords: Cell Adhesion; Development; E-cadherin; EMT; Gastrulation; Transcription/Developmental Factors