Regulation of Müllerian Duct Mesenchyme Transcription during Mammalian Sex Differentiation

Author

• Haowen Li, The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical SciencesFollow
• Richard R Behringer
• Rachel D Mullen

Author ORCID Identifier

https://orcid.org/0009-0004-7525-853X

Date of Graduation

8-2026

Document Type

Thesis (MS)

Program Affiliation

Genetics and Epigenetics

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Richard R. Behringer

Committee Member

Abhinav K. Jain

Committee Member

Rachel K. Miller

Committee Member

Ross A. Poché

Committee Member

Yoshihiro Komatsu

Abstract

Sp7/Osterix (Osx) encodes a zinc-finger transcription factor of the Specificity-protein family discovered by Nakashima et al. at the MD Anderson Cancer Center. While primarily recognized for its role in osteogenesis, Osx has also been implicated in mammalian reproductive development, particularly in male sex differentiation, where Müllerian Duct (MD) regression occurs, mediated by anti-Müllerian hormone (AMH) signaling. AMH-induced regression signals are transduced by the mesenchymal tissue surrounding the ductal structure, known as the Müllerian Duct mesenchyme (MDM). It was discovered that AMH signaling is necessary and sufficient for driving Osx expression in MDM. A previous transgenic mouse reporter assay identified a ~39 kb DNA fragment, encompassing the Osx locus, sufficient for driving male-specific expression patterns of a fluorescent reporter gene in embryonic MDM. However, the understanding of the regulatory mechanisms and functional significance of Osx in MDM, MD regression, and male sex differentiation remain incomplete. Evidence suggests that Osx is subject to cis-regulatory control by bone-specific enhancer binding during mammalian skeletal development. A tissue-specific cis-regulatory region directing Osx expression in MDM is suspected to exist within the ~39 kb fragment. Candidate regulatory regions upstream (~24 kb) and downstream (~5 kb) of the Osx coding sequence were isolated to generate transgenic reporter mouse lines to assess MDM-specific activity. In parallel, bulk ATAC-seq was performed on MDM isolated from embryonic day 14.5 (E14.5) male mice to map open chromatin domains within the locus and identify potential transcription factor binding sites. This integrated in vivo and bioinformatic approach should define the cis-regulatory landscape governing Osx expression in MDM, providing insight into mechanisms of male sex differentiation. The findings would establish a foundation for future MD-specific genetic manipulations, with implications for furthering our understanding of reproductive developmental biology and disease modeling.

Recommended Citation

Li, Haowen; Behringer, Richard R; and Mullen, Rachel D, "Regulation of Müllerian Duct Mesenchyme Transcription during Mammalian Sex Differentiation" (2026). Dissertations and Theses (Open Access). 1582.
https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1582

Keywords

Sp7, Osx, Embryogenesis, Müllerian duct, AMHR2, AMH, reproductive development, cis-regulation, enhancer, atac-seq