Lim1 is a homeobox gene expressed in the organizer region of mouse embryos. To investigate the role of Lim1 during embryogenesis, a targeted deletion of the Lim1 gene was generated in embryonic stem cells. Embryos homozygous for the null allele lacked anterior head structures but the remaining body axis developed normally. A partial secondary axis developed anteriorly in some mutant embryos. Lim1 is thus an essential regulator of the vertebrate head organizer.

The anterior visceral endoderm plays a pivotal role in establishing anterior-posterior polarity of the mouse embryo, but the molecular nature of the signals required remains to be determined. Here, we demonstrate that Cerberus-like(-/-);Lefty1(-/-) compound mutants can develop a primitive streak ectopically in the embryo. This defect is not rescued in chimeras containing wild-type embryonic, and Cerberus-like(-/-);Lefty1(-/-) extraembryonic, cells but is rescued in Cerberus-like(-/-); Lefty1(-/-) embryos after removal of one copy of the Nodal gene. Our findings provide support for a model whereby Cerberus-like and Lefty1 in the anterior visceral endoderm restrict primitive streak formation to the posterior end of mouse embryos by antagonizing Nodal signaling. Both antagonists are also required for proper patterning of the primitive streak.

Patterning of the mouse embryo along the anteroposterior axis during body plan development requires migration of the distal visceral endoderm (DVE) towards the future anterior side by a mechanism that has remained unknown. Here we show that Nodal signalling and the regionalization of its antagonists are required for normal migration of the DVE. Whereas Nodal signalling provides the driving force for DVE migration by stimulating the proliferation of visceral endoderm cells, the antagonists Lefty1 and Cerl determine the direction of migration by asymmetrically inhibiting Nodal activity on the future anterior side.

Lim1 encodes a LIM-class homeodomain transcription factor that is essential for head and kidney development. In the developing urogenital system, Lim1 expression has been documented in the Wolffian(mesonephric) duct, the mesonephros, metanephros and fetal gonads. Using, a Lim1 lacZ knock-in allele in mice, we identified a previously unreported urogenital tissue for Lim1 expression, the epithelium of the developing Müllerian duct that gives rise to the oviduct, uterus and upper region of the vagina of the female reproductive tract. Lim1expression in the Müllerian duct is dynamic, corresponding to its formation and differentiation in females and regression in males. Although female Lim1-null neonates had ovaries they lacked a uterus and oviducts. A novel female mouse chimera assay was developed and revealed that Lim1 is required cell autonomously for Müllerian duct epithelium formation. These studies demonstrate an essential role for Lim1 in female reproductive tract development.