title: Lhx1 is required in Müllerian duct epithelium for uterine development.
abstract: The female reproductive tract organs of mammals, including the oviducts, uterus, cervix and upper vagina, are derived from the Müllerian ducts, a pair of epithelial tubes that form within the mesonephroi. The Müllerian ducts form in a rostral to caudal manner, guided by and dependent on the Wolffian ducts that have already formed. Experimental embryological studies indicate that caudal elongation of the Müllerian duct towards the urogenital sinus occurs in part by proliferation at the ductal tip. The molecular mechanisms that regulate the elongation of the Müllerian duct are currently unclear. Lhx1 encodes a LIM-homeodomain transcription factor that is essential for male and female reproductive tract development. Lhx1 is expressed in both the Wolffian and Müllerian ducts. Wolffian duct-specific knockout of Lhx1 results in degeneration of the Wolffian duct and consequently the non-cell-autonomous loss of the Müllerian duct. To determine the role of Lhx1 specifically in the Müllerian duct epithelium, we performed a Müllerian duct-specific knockout study using Wnt7a-Cre mice. Loss of Lhx1 in the Müllerian duct epithelium led to a block in Müllerian duct elongation and uterine hypoplasia characterized by loss of the entire endometrium (luminal and glandular epithelium and stroma) and inner circular but not the outer longitudinal muscle layer. Time-lapse imaging and molecular analyses indicate that Lhx1 acts cell autonomously to maintain ductal progenitor cells for Müllerian duct elongation. These studies identify LHX1 as the first transcription factor that is essential in the Müllerian duct epithelial progenitor cells for female reproductive tract development. Furthermore, these genetic studies demonstrate the requirement of epithelial-mesenchymal interactions for uterine tissue compartment differentiation.
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Cheng-Chiu
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Grant D
authors.initials: GD
authors.lastname: Orvis
authors.affiliation: Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, PR China.
authors.forename: Kin Ming
authors.initials: KM
authors.lastname: Kwan
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: rrb@mdanderson.org.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Behringer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D019426:Integrases / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009095:Mullerian Ducts / Q000378:metabolism*; D038081:Organogenesis; D051762:PAX2 Transcription Factor / Q000378:metabolism; D059008:Time-Lapse Imaging; D014157:Transcription Factors / Q000378:metabolism*; D014599:Uterus / Q000196:embryology* / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase
keywords: Lhx1; Live imaging; Müllerian duct; Uterus; Wnt7a