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  current news   Press   selected story    
     
  14th April  
 

Early Embryonic Lethality of Mice Lacking ZO-2, but Not ZO-3, Reveals Critical and Nonredundant Roles for Individual Zonula Occludens Proteins in Mammalian Development.

 
 




Authors
Jianliang Xu, P. Jaya Kausalya, Dominic C. Y. Phua, Safiah Mohamed Ali, Zakir Hossain, and Walter Hunziker.

Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Republic of Singapore.

Correspondence should be addressed to Walter Hunziker: hunziker@imcb.a-star.edu.sg

Abstract
ZO-1, ZO-2, and ZO-3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton. Even though the zonula occludens (ZO) proteins are among the first TJ proteins to have been identified and have undergone extensive biochemical analysis, little is known about the physiological roles of individual ZO proteins in different tissues or during vertebrate development. Here, we show that ZO-3 knockout mice lack an obvious phenotype. In contrast, embryos deficient for ZO-2 die shortly after implantation due to an arrest in early gastrulation. ZO-2(-)(/)(-) embryos show decreased proliferation at embryonic day 6.5 (E6.5) and increased apoptosis at E7.5 compared to wild-type embryos. The asymmetric distribution of prominin and E-cadherin to the apical and lateral plasma membrane domains, respectively, is maintained in cells of ZO-2(-)(/)(-) embryos. However, the architecture of the apical junctional complex is altered, and paracellular permeability of a low-molecular-weight tracer is increased in ZO-2(-/-) embryos. Leaky TJs and, given the association of ZO-2 with connexins and several transcription factors, effects on gap junctions and gene expression, respectively, are likely causes for embryonic lethality. Thus, ZO-2 is required for mouse embryonic development, but ZO-3 is dispensable. This is to our knowledge the first report showing that an individual ZO protein plays a nonredundant and critical role in mammalian development.

 
 



 
 

Figure & Legend: Postimplantation development of ZO-2-/- embryos. Histology of embryos with typical normal or abnormal appearance at E5.5 (A, B), E6.5 (C, D), E7.5 (E, F) and E8.5 (G, H). Note the developmental arrest of ZO-2-/- embryos from E5.5 onwards and eventual resorption. epc, extraplacental cone; ac, amniotic cavity, ecc, exocoelomic cavity; epca, ectoplacental cavity; ne, neural ectoderm.

Published in Molecular and Cellular Biology (2008) Mar;28(5):1669-78

For more information on Walter Hunziker’s Lab, Please Click here.