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Molecular Endocrinology, doi:10.1210/me.2003-0403
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Molecular Endocrinology 18 (5): 1238-1250
Copyright © 2004 by The Endocrine Society

Uterine Msx-1 and Wnt4 Signaling Becomes Aberrant in Mice with the Loss of Leukemia Inhibitory Factor or Hoxa-10: Evidence for a Novel Cytokine-Homeobox-Wnt Signaling in Implantation

Takiko Daikoku, Haengseok Song, Yong Guo, Anne Riesewijk, Sietse Mosselman, Sanjoy K. Das and Sudhansu K. Dey

Departments of Pediatrics (T.D., H.S., Y.G., S.K.Da., S.K.De.), Cell and Developmental Biology and Pharmacology (S.K.De.), Vanderbilt University Medical Center, Nashville, Tennessee 37232; and Target Discovery and Department of Pharmacology (A.R., S.M.), NV Organon, 5340 BH Oss, The Netherlands

Address all correspondence and requests for reprints to: Sudhansu K. Dey, Vanderbilt University Medical Center, Developmental Biology, MCN-D4100, Nashville, Tennessee 37232-2678. E-mail: sk.dey{at}vanderbilt.edu.

Successful implantation absolutely depends on the reciprocal interaction between the implantation-competent blastocyst and the receptive uterus. Expression and gene targeting studies have shown that leukemia inhibitory factor (LIF), a cytokine of the IL-6 family, and Hoxa-10, an abdominalB-like homeobox gene, are crucial to implantation and decidualization in mice. Using these mutant mice, we sought to determine the importance of Msx-1 (another homeobox gene formerly known as Hox-7.1) and of Wnt4 (a ligand of the Wnt family) signaling in implantation because of their reported functions during development. We observed that Msx-1, Wnt4, and a Wnt antagonist sFRP4 are differentially expressed in the mouse uterus during the periimplantation period, suggesting their role in implantation. In addition, we observed an aberrant uterine expression of Msx-1 and sFRP4 in Lif mutant mice, and of Wnt4 and sFRP4 in Hoxa-10 mutant mice, further reinforcing the importance of these signaling pathways in implantation. Collectively, the present results provide evidence for a novel cytokine-homeotic-Wnt signaling network in implantation.




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