Mesenchymal-to-epithelial transitions require tissue-specific interactions with distinct laminins.
Animals
Animals, Genetically Modified
COP-Coated Vesicles
/ genetics
Cadherins
/ genetics
Cell Movement
Cell Polarity
Digestive System
/ embryology
Drosophila Proteins
/ genetics
Drosophila melanogaster
/ embryology
Epithelial Cells
/ metabolism
Epithelial-Mesenchymal Transition
GATA Transcription Factors
/ genetics
Gene Expression Regulation, Developmental
Integrin alpha Chains
/ genetics
Intracellular Signaling Peptides and Proteins
/ genetics
Laminin
/ genetics
Microscopy, Confocal
Microscopy, Fluorescence
Signal Transduction
Time Factors
Time-Lapse Imaging
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
02 08 2021
02 08 2021
Historique:
received:
26
10
2020
revised:
29
03
2021
accepted:
10
05
2021
entrez:
28
5
2021
pubmed:
29
5
2021
medline:
21
10
2021
Statut:
ppublish
Résumé
Mesenchymal-to-epithelial transition (MET) converts cells from migratory mesenchymal to polarized epithelial states. Despite its importance for both normal and pathological processes, very little is known about the regulation of MET in vivo. Here we exploit midgut morphogenesis in Drosophila melanogaster to investigate the mechanisms underlying MET. We show that down-regulation of the EMT transcription factor Serpent is required for MET, but not sufficient, as interactions with the surrounding mesoderm are also essential. We find that midgut MET relies on the secretion of specific laminins via the CopII secretory pathway from both mesoderm and midgut cells. We show that secretion of the laminin trimer containing the Wingblister α-subunit from the mesoderm is an upstream cue for midgut MET, leading to basal polarization of αPS1 integrin in midgut cells. Polarized αPS1 is required for the formation of a monolayered columnar epithelium and for the apical polarization of αPS3, Baz, and E-Cad. Secretion of a distinct LamininA-containing trimer from midgut cells is required to reinforce the localization of αPS1 basally, and αPS3 apically, for robust repolarization. Our data suggest that targeting these MET pathways, in conjunction with therapies preventing EMT, may present a two-pronged strategy toward blocking metastasis in cancer.
Identifiants
pubmed: 34047771
pii: 212200
doi: 10.1083/jcb.202010154
pmc: PMC8167899
pii:
doi:
Substances chimiques
Cadherins
0
Drosophila Proteins
0
GATA Transcription Factors
0
Integrin alpha Chains
0
Intracellular Signaling Peptides and Proteins
0
Laminin
0
alpha PS3 integrin, Drosophila
0
baz protein, Drosophila
0
shg protein, Drosophila
0
srp protein, Drosophila
0
wb protein, Drosophila
0
laminin A
151186-83-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204615/Z/16/Z
Pays : United Kingdom
Informations de copyright
© 2021 Pitsidianaki et al.
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