A histological study was performed on serially sectioned human and mouse em
bryos to study the influences of programmed cell death (PCD) during morphog
enesis for clarifying the existing controversies on the morphology and basi
c processes involved in the embryonic development of the male anterior uret
hra. The following new insights into the development of the anterior urethr
a could be established. The formation of the urethra starts with the early
adhesion of the arms of the genital tubercle. In this way an epithelial pla
te is formed, located in the ventral midline, that is in continuity with th
e cloacal membrane. Male sex differentiation takes place following rupture
of this cloacal membrane through programmed cell death. Fusion of the uroge
nital swellings with primary luminization gives rise to the penile urethra,
whereas the glandular part of the urethra is formed through secondary lumi
nization of the epithelial cord that is formed during fusion of the arms of
the genital tubercle, i.e., the glans. In both fusion processes, apoptosis
plays a key role. The consequence of fusion of the urogenital swellings is
that their mesodermal cores unite on the ventral aspect of the penile uret
hra, where they differentiate into the integumental structures. The prepuce
starts to develop as a fold of ectoderm with a mesodermal core after compl
ete fusion of the entire urethra. Finally, the scrotum was found to develop
through merging of the labioscrotal swellings and not by fusion. (C) 2000
Wiley-Liss, Inc.