First Author | Huang CC | Year | 2014 |
Journal | Dev Biol | Volume | 389 |
Issue | 2 | Pages | 124-36 |
PubMed ID | 24560999 | Mgi Jnum | J:208898 |
Mgi Id | MGI:5565160 | Doi | 10.1016/j.ydbio.2014.01.025 |
Citation | Huang CC, et al. (2014) Lhx1 is required in Mullerian duct epithelium for uterine development. Dev Biol 389(2):124-36 |
abstractText | The female reproductive tract organs of mammals, including the oviducts, uterus, cervix and upper vagina, are derived from the Mullerian ducts, a pair of epithelial tubes that form within the mesonephroi. The Mullerian 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 Mullerian duct towards the urogenital sinus occurs in part by proliferation at the ductal tip. The molecular mechanisms that regulate the elongation of the Mullerian 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 Mullerian ducts. Wolffian duct-specific knockout of Lhx1 results in degeneration of the Wolffian duct and consequently the non-cell-autonomous loss of the Mullerian duct. To determine the role of Lhx1 specifically in the Mullerian duct epithelium, we performed a Mullerian duct-specific knockout study using Wnt7a-Cre mice. Loss of Lhx1 in the Mullerian duct epithelium led to a block in Mullerian 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 Mullerian duct elongation. These studies identify LHX1 as the first transcription factor that is essential in the Mullerian 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. |