8 / 492
13:36 - 13:39
S1-3
(PP)
TESTING THE URETERIC BUD THEORY
Julia FINKELSTEIN
1
and Cathy MENDELSOHN
2
1) Columbia University College of Physicians & Surgeons, Urology, New York, USA - 2) Columbia University College of
Physicians & Surgeons, Department of Urology, Genetics & Development and Pathology, New York, USA
PURPOSE
During development, each component of the genitourinary (GU) tract must join in a stereotypical way to produce a
functional urinary outflow tract. The anatomy of this system is complex and changes rapidly throughout embryonic
development. Congenital anomalies of the kidney and urinary tract (CAKUT) are common and represent a substantial
source of morbidity in children. There are limited publications on human developmental anatomy and great reliance has
been placed on animal models, primarily the mouse. We sought to analyze human embryos to establish detailed
information on the development of the GU system.
MATERIAL AND METHODS
With institutional review board approval, human embryos were serially sectioned and representative sections were
stained with hematoxylin and eosin for histological analysis. For immunohistochemistry, primary antibodies to p63,
caspase-3, PAX-2, upk, krt5, FoxA2, and e-cadherin were used. Because the structures and developmental pathways of
the mouse are known, we compared human embryos to equivalent stages in mouse.
RESULTS
Insertion of the nephric ducts (NDs) into the cloaca occurs at approximately 3 weeks in humans (embryonic day 9 in
mouse), creating a connection between the upper and lower urinary tracts. The ureteric bud emerges from the posterior
aspect of the NDs shortly after. The ureters are joined to the most posterior ND segment, known as the the common
nephric duct (CND). The CND in humans appear to be larger that in mouse. The CND does not differentiate into the
bladder trigone but rather undergoes apoptosis, contradicting the Ureteric Bud Theory of Mackie and Stephens. This
apoptosis occurs near the sinus ridge, a raised epithelial structure situated at the dorsal aspect of the urogenital sinus.
Signals from this site may be important for normal ureteral insertion.
CONCLUSIONS
This research is an important basis for understanding human GU tract anatomy and development and will be critical for
understanding the basis of CAKUT.