Early embryonic death in mice lacking the beta-catenin-binding protein Duplin.

Abstract:

:The Wnt signaling pathway plays a pivotal role in vertebrate early development and morphogenesis. Duplin (axis duplication inhibitor) interacts with beta-catenin and prevents its binding to Tcf, thereby inhibiting downstream Wnt signaling. Here we show that Duplin is expressed predominantly from early- to mid-stage mouse embryogenesis, and we describe the generation of mice deficient in Duplin. Duplin(-/-) embryos manifest growth retardation from embryonic day 5.5 (E5.5) and developmental arrest accompanied by massive apoptosis at E7.5. The mutant embryos develop into an egg cylinder but do not form a primitive streak or mesoderm. Expression of beta-catenin target genes, including those for T (brachyury), Axin2, and cyclin D1, was not increased in Duplin(-/-) embryos, suggesting that the developmental defect is not simply attributable to upregulation of Wnt signaling caused by the lack of this inhibitor. These results suggest that Duplin plays an indispensable role, likely by a mechanism independent of inhibition of Wnt signaling, in mouse embryonic growth and differentiation at an early developmental stage.

journal_name

Mol Cell Biol

authors

Nishiyama M,Nakayama K,Tsunematsu R,Tsukiyama T,Kikuchi A,Nakayama KI

doi

10.1128/MCB.24.19.8386-8394.2004

subject

Has Abstract

pub_date

2004-10-01 00:00:00

pages

8386-94

issue

19

eissn

0270-7306

issn

1098-5549

pii

24/19/8386

journal_volume

24

pub_type

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