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Updated: Jul 10, 2026
Identification, Histological Characterization, and Dissection of Mouse Prostate Lobes for In Vitro 3D Spheroid Culture Models
Published on: September 18, 2018
Noggin is required for normal lobe patterning and ductal budding in the mouse prostate
Crist Cook1, Chad M Vezina, Sarah H Allgeier
1Department of Surgery, University of Wisconsin, Box 3236 Clinical Science Center-G5, 600 Highland Ave., Madison, WI 53792, USA.
Abstract:
Mesenchymal expression of the BMP antagonist NOGGIN during prostate development plays a critical role in pre-natal ventral prostate development and opposes BMP4-mediated inhibition of cell proliferation during postnatal ductal development. Morphologic examination of newborn Noggin-/- male fetuses revealed genitourinary anomalies including cryptorchidism, incomplete separation of the hindgut from the urogenital sinus (UGS), absence of the ventral mesenchymal pad, and a complete loss of ventral prostate (VP) budding. Examination of lobe-specific marker expression in the E14 Noggin-/- UGS rescued by transplantation under the renal capsule of a male nude mouse confirmed a complete loss of VP determination. More modest effects were observed in the other lobes, including decreased number of ductal buds in the dorsal and lateral prostates of newborn Noggin-/- males. BMP4 and BMP7 have been shown to inhibit ductal budding and outgrowth by negatively regulating epithelial cell proliferation. We show here that NOGGIN can neutralize budding inhibition by BMP4 and rescues branching morphogenesis of BMP4-exposed UGS in organ culture and show that the effects of BMP4 and NOGGIN activities converge on P63+ epithelial cells located at nascent duct tips. Together, these studies show that the BMP-NOGGIN axis regulates patterning of the ventral prostate, regulates ductal budding, and controls proliferation of P63+ epithelial cells in the nascent ducts of developing mouse prostate.
Insights
The BMP-NOGGIN axis is crucial for mouse prostate development. Loss of NOGGIN causes severe genitourinary anomalies and ventral prostate absence, while NOGGIN counteracts BMP4 to promote ductal budding.
Area of Science:
- Developmental Biology
- Urology
- Molecular Biology
Background:
- Mesenchymal NOGGIN is vital for prostate development, opposing BMP4's inhibition of cell proliferation.
- BMP4 and BMP7 inhibit ductal budding and outgrowth by negatively regulating epithelial cell proliferation.
Purpose of the Study:
- To investigate the role of the BMP-NOGGIN axis in prostate development.
- To elucidate the mechanism by which NOGGIN influences BMP4-mediated effects on prostate ductal budding and epithelial cell proliferation.
Main Methods:
- Morphological examination of newborn Noggin-/- male fetuses.
- Transplantation of E14 Noggin-/- urogenital sinus (UGS) into nude mice.
- Organ culture of BMP4-exposed UGS to assess NOGGIN's effect.
Main Results:
- Noggin-/- male fetuses exhibited genitourinary anomalies, including cryptorchidism and complete loss of ventral prostate budding.
- Transplantation confirmed a complete loss of ventral prostate determination in Noggin-/- UGS.
- NOGGIN neutralized BMP4-induced inhibition of ductal budding and rescued branching morphogenesis in organ culture.
- BMP4 and NOGGIN activities converge on P63+ epithelial cells at nascent duct tips.
Conclusions:
- The BMP-NOGGIN axis is essential for ventral prostate patterning and ductal budding in mice.
- NOGGIN antagonizes BMP4 to regulate epithelial cell proliferation and branching morphogenesis during prostate development.
- This axis specifically impacts P63+ epithelial cells in developing prostate ducts.
