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doi: 10.1242/10.1242/dev.00225


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Development 130, 495-505 (2003)
Copyright © 2003 The Company of Biologists Limited

Functional ablation of the mouse Ldb1 gene results in severe patterning defects during gastrulation

Mahua Mukhopadhyay1,*, Andreas Teufel1,*, Tsuyoshi Yamashita1,*,{dagger}, Alan D. Agulnick1,{ddagger}, Lan Chen1, Karen M. Downs2, Alice Schindler1, Alexander Grinberg1, Sing-Ping Huang1, David Dorward3 and Heiner Westphal1,§

1 Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
2 Department of Anatomy, University of Wisconsin-Madison Medical School, Madison, WI 53706, USA
3 National Institutes of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA
{dagger} Present address: Department of Obstetrics and Gynecology, Asahikawa Medical College, Nishikagura 4-5-3-11, Asahikawa, Japan
{ddagger} Present address: CyThera Inc., 3550 General Atomics Court, San Diego, CA 92121, USA

§ Author for correspondence (e-mail: hw{at}helix.nih.gov)

Accepted 18 October 2002

The LIM domain-binding protein 1 (Ldb1) is found in multi-protein complexes containing various combinations of LIM-homeodomain, LIM-only, bHLH, GATA and Otx transcription factors. These proteins exert key functions during embryogenesis. Here we show that targeted deletion of the Ldb1 gene in mice results in a pleiotropic phenotype. There is no heart anlage and head structures are truncated anterior to the hindbrain. In about 40% of the mutants, posterior axis duplication is observed. There are also severe defects in mesoderm-derived extraembryonic structures, including the allantois, blood islands of the yolk sack, primordial germ cells and the amnion. Abnormal organizer gene expression during gastrulation may account for the observed axis defects in Ldb1 mutant embryos. The expression of several Wnt inhibitors is curtailed in the mutant, suggesting that Wnt pathways may be involved in axial patterning regulated by Ldb1.

Key words: Ldb1, Wnt inhibitor(s), Otx2, Mouse, Anterior-posterior axis




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