Hedgehog signaling is required for endometrial remodeling and myometrial homeostasis in the cycling mouse uterus
Elle C. Roberson,
Ngan Kim Tran,
Anushka N. Godambe,
Harrison Mark,
Michelle Nguimtsop,
Trinity Rust,
Elizabeth Ung,
LeCaine J. Barker,
Rebecca D. Fitch,
John B. Wallingford
Affiliations
Elle C. Roberson
Department of Pediatrics, Section of Developmental Biology, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA; Corresponding author
Ngan Kim Tran
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
Anushka N. Godambe
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
Harrison Mark
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
Michelle Nguimtsop
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
Trinity Rust
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
Elizabeth Ung
Department of Pediatrics, Section of Developmental Biology, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA
LeCaine J. Barker
Department of Pediatrics, Section of Developmental Biology, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA
Rebecca D. Fitch
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
John B. Wallingford
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA; Corresponding author
Summary: Decades of work demonstrate that the mammalian estrous cycle is controlled by cycling steroid hormones. However, the signaling mechanisms that act downstream, linking hormonal action to the physical remodeling of the cycling uterus, remain unclear. To address this issue, we analyzed gene expression at all stages of the mouse estrous cycle. Strikingly, we found that several genetic programs well-known to control tissue morphogenesis in developing embryos displayed cyclical patterns of expression. We find that most of the genetic architectures of Hedgehog signaling (ligands, receptors, effectors, and transcription factors) are transcribed cyclically in the uterus, and that conditional disruption of the Hedgehog receptor smoothened not only elicits a failure of normal cyclical thickening of the endometrial lining but also induces aberrant deformation of the uterine smooth muscle. Together, our data shed light on the mechanisms underlying normal uterine remodeling specifically and cyclical gene expression generally.
