Functional ablation of the mouseLdb1gene results in severe patterning defects during gastrulation
Author:
Mukhopadhyay Mahua1, Teufel Andreas1, Yamashita Tsuyoshi12, Agulnick Alan D.13, Chen Lan1, Downs Karen M.4, Schindler Alice1, Grinberg Alexander1, Huang Sing-Ping1, Dorward David5, Westphal Heiner1
Affiliation:
1. Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda,Maryland 20892, USA 2. Present address: Department of Obstetrics and Gynecology, Asahikawa Medical College, Nishikagura 4-5-3-11, Asahikawa, Japan 3. Present address: CyThera Inc., 3550 General Atomics Court, San Diego, CA 92121, USA 4. Department of Anatomy, University of Wisconsin-Madison Medical School,Madison, WI 53706, USA 5. National Institutes of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA
Abstract
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.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference84 articles.
1. Acampora, D., Mazan, S., Lallemand, Y., Avantaggiato, V., Maury,M., Simeone, A. and Brulet, P. (1995). Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation.Development121,3279-3290. 2. Acampora, D., Avantaggiato, V., Tuorto, F., Briata, P., Corte,G. and Simeone, A. (1998). Visceral endoderm-restricted translation of Otx1 mediates recovery of Otx2 requirements for specification of anterior neural plate and normal gastrulation.Development125,5091-5104. 3. Agulnick, A. D., Taira, M., Breen, J. J., Tanaka, T., Dawid, I. B. and Westphal, H. (1996). Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins.Nature384,270-272. 4. Andree, B., Duprez, D., Vorbusch, B., Arnold, H. H. and Brand,T. (1998). BMP-2 induces ectopic expression of cardiac lineage markers and interferes with somite formation in chicken embryos.Mech. Dev.70,119-131. 5. Ang, S. L., Conlon, R. A., Jin, O. and Rossant, J.(1994). Positive and negative signals from mesoderm regulate the expression of mouse Otx2 in ectoderm explants.Development120,2979-2989.
Cited by
130 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|