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

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

Communications biology (2022-04-21)
Chiharu Kimura-Yoshida, Kyoko Mochida, Shin-Ichiro Kanno, Isao Matsuo
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Wnt Agonist, The Wnt Agonist, also referenced under CAS 853220-52-7, controls the biological activity of Wnt. This small molecule/inhibitor is primarily used for Cancer applications.
Sigma-Aldrich
Anti-USP39 antibody produced in rabbit, affinity isolated antibody