# GUDMAP: Mapping molecular regionalization of cell types along the anterior-posterior axis of the urethra

> **NIH NIH U01** · UNIVERSITY OF FLORIDA · 2020 · $396,911

## Abstract

Project Summary
 In mammals, the urethra is the sole pathway for excretion of urine from the body and it is the primary
point of entry for lower urinary tract infections and sexually transmitted diseases. Urethral malformations are
among the most common birth defects in humans, yet our understanding of the molecular development of the
urethra lags years, perhaps decades, behind other systems, such as the CNS, gut, and limbs. The anterior to
posterior (A-P) axis of the urethra extends from the bladder to the urethral meatus, which opens at the tip of
the penis in males or between the vaginal opening and the clitoris in females. At the cell and tissue levels, the
urethral tube shows extensive heterogeneity along its A-P axis. Epithelial structure varies along this axis, with
the linings of the pre-prostatic, prostatic, membranous, and penile urethra each having a distinctive character.
Moreover, morphogenetic processes occur at discrete A-P positions along the urogenital sinus. For example,
the accessory sex glands, such as the prostate and bulbourethral glands bud off the urogenital sinus at specific
axial levels. Muscular sphincters also develop at highly localized regions. Despite this extensive anatomical
regionalization, the molecular anatomy that establishes these patterns is not understood. In addition to this
developmental significance, A-P identity of cells may influence adult function. Do male-female differences in
cell type identity and molecular immunologic profiles along the A-P axis of the uretha influence colonization
of the urethra and bladder by pathogens? Here we propose that specification of cell type identity along the
urogenital sinus can be approached as a fundamental developmental problem of A-P regionalization.
Analogous processes have been studied extensively in the gastrointestinal tract, resulting in a detailed picture
of gut regionalization, sphincter development, specification of the positions and identities of organs, and
control of cell type identities within those organs. Building on our GUDMAP2 project, which focused on the
dorsoventral (D-V) axis of the LUT, this study aims to identify and map the molecular regionalization of cells
along the A-P axis of the mouse and human urethra, from the bladder to the urethral meatus. We will use laser
capture microdissection to isolate urethral cells from the pre-prostatic, prostatic, membranous, and penile
regions of mouse and human urethra and use RNAseq to identify their transcriptional profiles. We will then
carry out a comparative in situ hybridization analysis of mouse and human urethrae in sections and whole
mounts, and we will use Optical Projection Tomography to map A-P patterns of gene expression in 3D. Our
goal is to generate the foundation of gene expression data necessary for the urology research community to
study how cell type identity along the urethra relates to development of congenital defects and to disease.

## Key facts

- **NIH application ID:** 9944527
- **Project number:** 5U01DK110812-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** MARTIN J COHN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,911
- **Award type:** 5
- **Project period:** 2016-09-15 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944527

## Citation

> US National Institutes of Health, RePORTER application 9944527, GUDMAP: Mapping molecular regionalization of cell types along the anterior-posterior axis of the urethra (5U01DK110812-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9944527. Licensed CC0.

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