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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2013 July 12; 288(28): 20121.
PMCID: PMC3711280

Discovery of a Novel Player in Cell Polarity during Embryogenesis♦

SEC14 and Spectrin Domains 1 (Sestd1) and Dapper Antagonist of Catenin 1 (Dact1) Scaffold Proteins Cooperatively Regulate the Van Gogh-like 2 (Vangl2) Four-pass Transmembrane Protein and Planar Cell Polarity (PCP) Pathway during Embryonic Development in Mice

♦ See referenced article, J. Biol. Chem. 2013, 288, 20111–20120

During embryogenesis, the planar cell polarity (PCP) pathway oversees cell polarity and polarized cell movements. PCP is a conserved branch of developmentally and clinically important Wnt intercellular signaling. If PCP components are not functioning in mice, the animals suffer from developmental problems such as improper neural tube closure, and pathway abnormalities similarly underlie a broad class of birth defects in humans. In this Paper of the Week, XiaoYong Yang and Benjamin Cheyette at the University of California, San Francisco, describe finding a novel binding partner called Sestd1, which interacts with two major components of the PCP pathway, Vangl2 and Dact1. If Sestd1 is missing, the mice suffer from the same developmental defects as if Dact1 were missing. The investigators found that a complex including Sestd1 and Dact1 regulates Rho GTPase activity, and they established with genetic methods that, like Dact1, Sestd1 also regulates Vangl2. They concluded, “The discovery of PCP pathway regulators and components uncovers molecular mechanisms contributing to neural tube defects, other birth defects, and disease processes in humans.”

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Loss of Sestd1 causes defects that resemble a loss of Dact1.

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