# Molecular Basis of Sexually Dimorphic Development of the Genital Tubercle

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2021 · $345,600

## Abstract

An important feature of mammals is the sexually dimorphic reproductive tracts, which include external and
internal sex organs. Abnormal development of the genital tubercle (GT), the common embryonic precursor of
both male and female external genitalia, frequently results in birth defects including ambiguous genitalia and
hypospadias but the underlying molecular basis is poorly understood. This proposal focuses on formation of
the external genitalia, a significantly understudied area of embryology. Based on our preliminary data, we
hypothesize that, in addition to the gonad-derived sex hormones such as androgens, Wnts expressed from
the GT epithelium function as the permissive signal and; following the Wnt and androgen stimulation the
gender-specific genomic activity of GT mesenchyme leads to formation of gender-specific external genital
structures. We have designed three specific aims to test this hypothesis: 1) to examine whether Wnt4 is the
permissive signal for dimorphic GT differentiation; 2) to determine whether sex hormones reprogram the GT-
specific landscape of transcription enhancers to control dimorphic gene expression; and 3) to identify critical
GT-specific downstream effectors of sex hormones that induce dimorphic GT differentiation to form penis in
males and clitoris in females. We have developed and validated a suite of innovative genetic and genomic
tools in order to achieve these specific aims. Findings from the proposed studies are expected to improve our
understanding of sexual dimorphism in mammals, and to shed new light on the pathogenesis of common birth
defects including ambiguous genitalia and hypospadias.

## Key facts

- **NIH application ID:** 10362116
- **Project number:** 7R01DK110477-05
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Xue Sean Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,600
- **Award type:** 7
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10362116

## Citation

> US National Institutes of Health, RePORTER application 10362116, Molecular Basis of Sexually Dimorphic Development of the Genital Tubercle (7R01DK110477-05). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10362116. Licensed CC0.

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