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Previously, we have shown that the translocation of Grainyhead-like 3 (GRHL3) transcription factor from the nucleus to the cytoplasm triggers the switch from canonical Wnt signaling for epidermal differentiation to non-canonical Wnt signaling for epithelial morphogenesis. However, the molecular mechanism that underlies the cytoplasmic localization of GRHL3 protein and that activates non-canonical Wnt signaling is not known. Here, we show that ubiquitin-specific protease 39 (USP39), a deubiquitinating enzyme, is involved in the subcellular localization of GRHL3 as a potential GRHL3-interacting protein and is necessary for epithelial morphogenesis to up-regulate expression of planar cell polarity (PCP) components. Notably, mouse Usp39-deficient embryos display early embryonic lethality due to a failure in primitive streak formation and apico-basal polarity in epiblast cells, resembling those of mutant embryos of the Prickle1 gene, a crucial PCP component. Current findings provide unique insights into how differentiation and morphogenesis are coordinated to construct three-dimensional complex structures via USP39.

Titel:	USP39 is essential for mammalian epithelial morphogenesis through upregulation of planar cell polarity components.
Autor/in / Beteiligte Person:	Kimura-Yoshida, C ; Mochida, K ; Kanno, SI ; Matsuo, I
Zeitschrift:	Communications biology, Jg. 5 (2022-04-19), Heft 1, S. 378
Veröffentlichung:	London, United Kingdom : Nature Publishing Group UK, [2018]-, 2022
Medientyp:	academicJournal
ISSN:	2399-3642 (electronic)
DOI:	10.1038/s42003-022-03254-7
Schlagwort:	Adaptor Proteins, Signal Transducing metabolism Animals Cell Differentiation DNA-Binding Proteins metabolism LIM Domain Proteins Mammals Mice Morphogenesis Up-Regulation Cell Polarity physiology Transcription Factors metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Commun Biol] 2022 Apr 19; Vol. 5 (1), pp. 378. <i>Date of Electronic Publication: </i>2022 Apr 19. MeSH Terms: Cell Polarity* / physiology ; Transcription Factors* / metabolism ; Adaptor Proteins, Signal Transducing / metabolism ; Animals ; Cell Differentiation ; DNA-Binding Proteins / metabolism ; LIM Domain Proteins ; Mammals ; Mice ; Morphogenesis ; Up-Regulation References: Nat Rev Genet. 2003 Oct;4(10):784-93. (PMID: 13679871) ; Annu Rev Cell Dev Biol. 2002;18:463-93. (PMID: 12142280) ; Genes Dev. 1995 Dec 15;9(24):3177-89. (PMID: 8543160) ; Nat Cell Biol. 2014 Oct;16(10):1016-26, 1-8. (PMID: 25194926) ; Development. 2010 Apr;137(7):1067-73. (PMID: 20215345) ; Nat Neurosci. 2003 Mar;6(3):231-42. (PMID: 12577062) ; J Immunol. 2020 Dec 1;205(11):3167-3178. (PMID: 33127822) ; Genes Dev. 2019 Oct 1;33(19-20):1361-1366. 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(PMID: 30733604) Substance Nomenclature: 0 (Adaptor Proteins, Signal Transducing) ; 0 (DNA-Binding Proteins) ; 0 (Grhl3 protein, mouse) ; 0 (LIM Domain Proteins) ; 0 (Prickle1 protein, mouse) ; 0 (Transcription Factors) Entry Date(s): Date Created: 20220420 Date Completed: 20220421 Latest Revision: 20220716 Update Code: 20240513 PubMed Central ID: PMC9018712

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USP39 is essential for mammalian epithelial morphogenesis through upregulation of planar cell polarity components.