Molecular Genetics of Female Reproductive Tract

University Of Tx Md Anderson Can Ctr, Houston TX

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Abstract

The primary objective of this proposal is to understand the molecular mechanisms that regulate female reproductive tract organogenesis. Our preliminary studies indicate that the homeobox gene Liml and the gene encoding the M011erian inhibiting substance type II receptor Misr2 provide molecular entry points for dissecting the genetic pathways that regulate M011erian duct epithelium and mesenchyme development, respectively, for female reproductive tract formation. We propose molecular genetic studies to 1) visualize the cellular behavior of M011erian duct epithelium and mesenchyme during M011erian duct formation using time lapse imaging of differentially colored nuclear- and mitotic chromosome-tagged fluorescent proteins, 2) identify the cis-elements of the Liml and Misr2 genes that direct M011erian duct epithelium- and mesenchyme-specific transcription, respectively, 3) examine the role of the Wolffian duct in M011erian duct formation, 4) determine the role of Liml in female reproductive tract formation, and 5) define the signaling molecules that act in mesenchyme to mediate Mellerian inhibiting substance-induced M011erian duct regression using a novel conditional knockout strategy. Our proposed studies should provide new information about the molecular and cellular mechanisms that regulate female reproductive tract formation and its elimination during male fetal development.