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Genes Dev March 1, 2013; 27 (5): 491-503.

The Smurf ubiquitin ligases regulate tissue separation via antagonistic interactions with ephrinB1.

Hwang YS , Lee HS , Kamata T , Mood K , Cho HJ , Winterbottom E , Ji YJ , Singh A , Daar IO .

The formation of tissue boundaries is dependent on the cell-cell adhesion/repulsion system that is required for normal morphogenetic processes during development. The Smad ubiquitin regulatory factors (Smurfs) are E3 ubiquitin ligases with established roles in cell growth and differentiation, but whose roles in regulating cell adhesion and migration are just beginning to emerge. Here, we demonstrate that the Smurfs regulate tissue separation at mesoderm/ectoderm boundaries through antagonistic interactions with ephrinB1, an Eph receptor ligand that has a key role in regulating the separation of embryonic germ layers. EphrinB1 is targeted by Smurf2 for degradation; however, a Smurf1 interaction with ephrinB1 prevents the association with Smurf2 and precludes ephrinB1 from ubiquitination and degradation, since it is a substantially weaker substrate for Smurf1. Inhibition of Smurf1 expression in embryonic mesoderm results in loss of ephrinB1-mediated separation of this tissue from the ectoderm, which can be rescued by the coincident inhibition of Smurf2 expression. This system of differential interactions between Smurfs and ephrinB1 regulates the maintenance of tissue boundaries through the control of ephrinB protein levels.

PubMed ID: 23475958
PMC ID: PMC3605463
Article link: Genes Dev
Grant support: [+]
Genes referenced: bcr efnb1 efnb2 efnb3 h2bc21 mapk1 rhoa smad2 smurf1 smurf2 sult2a1
Morpholinos: smurf1 MO1 smurf2 MO1 smurf2 MO2

Article Images: [+] show captions
References [+] :
Alexandrova, Smurf1 regulates neural patterning and folding in Xenopus embryos by antagonizing the BMP/Smad1 pathway. 2006, Pubmed, Xenbase

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