Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling
2006
The urogenital and reproductive organs, including the external genitalia,
bladder and urethra, develop as anatomically aligned organs. Descriptive and
experimental embryology suggest that the cloaca, and its derivative, the
urogenital sinus, contribute to the formation of these organs. However, it is
unknown how the primary tissue lineages in, and adjacent to, the cloaca give
rise to the above organs, nor is bladder formation understood. While it is
known that sonic hedgehog (Shh) is expressed by the cloacal epithelia, the
developmental programs that regulate and coordinate the formation of the
urogenital and reproductive organs have not been elucidated. Here we report
that Shh mutant embryos display hypoplasia of external genitalia, internal
urethra (pelvic urethra) and bladder. The importance of Shh signaling in the
development of bladder and external genitalia was confirmed by analyzing a
variety of mutant mouse lines with defective hedgehog signaling. By
genetically labeling hedgehog-responding tissue lineages adjacent to the
cloaca and urogenital sinus, we defined the contribution of these tissues to
the bladder and external genitalia. We discovered that development of smooth
muscle myosin-positive embryonic bladder mesenchyme requires Shh signaling,
and that the bladder mesenchyme and dorsal (upper) external genitalia derive
from Shh-responsive peri-cloacal mesenchyme. Thus, the mesenchymal precursors
for multiple urogenital structures derive from peri-cloacal mesenchyme and the
coordination of urogenital organ formation from these precursors is
orchestrated by Shh signals.
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