Abstract: TH-PO0560
Odd-Skipped Related 1 Regulates Bladder Development
Session Information
- Development, Stem Cells, and Regenerative Medicine
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 600 Development, Stem Cells, and Regenerative Medicine
Authors
- Murugapoopathy, Vasikar, McGill University, Montreal, Quebec, Canada
- Gupta, Indra R., Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
Background
The bladder consists of the epithelium which acts as a barrier to urine, the extracellular matrix-rich lamina propria that bears the mechanical load, and the contractile smooth muscle that expels urine. The molecular mechanisms underlying formation of these layers is largely unresolved. The transcription factor, Odd-skipped related 1 (Osr1), is an essential regulator of kidney, heart, lung and limb development, where it interacts with hedgehog (Hh), Bmp, Wnt and Fgf signaling pathways. We hypothesize that Osr1 regulates embryonic bladder development.
Methods
Single-cell RNA sequencing (scRNAseq) with histological and immunofluorescent analyses were performed on wild-type and Osr1 KO mouse bladders at embryonic day (E)12 when the bladder first forms, E14 when smooth muscle arises, and E15 when the lamina propria, muscle and epithelium mature.
Results
Osr1 mRNAs are expressed throughout the developing bladder. Smooth muscle and lamina propria differentiation depends on Hh, Bmp, Wnt and Fgf signaling based on scRNAseq analysis of their cognate ligands and receptors. At E12, loss of Osr1 resulted in decreased smooth muscle progenitors, while at E14, there were increased mesenchymal cell progenitors that correlated with a lack of smooth muscle cells and fibroblasts. At E15, there was less smooth muscle, a lack of suburothelial cells, no extracellular matrix, and no epithelial stratification in Osr1 KO compared to wild-type bladders (Fig.1). The morphological changes in Osr1 KO bladders arise from downregulation of Hh, Bmp, Wnt and Fgf signaling pathways at E14 (Fig.2).
Conclusion
Osr1 regulates bladder patterning through interactions with Hh, Bmp, Wnt and Fgf signaling pathways.
Osr1 KO bladders have increased mesenchymal cell progenitors and depletion of smooth muscle and fibroblasts
Hh, Bmp, Wnt and Fgf signaling pathways are downregulated in Osr1 KO bladders
Funding
- Government Support – Non-U.S.