Hedgehog Signaling in Animal Development and Human Disease 215
Motoyama et al. 1998). There are, however, two interesting exceptions,
the developing testes and hair follicle.
12.2.3 ptc1 and ptc2 May Have Separate Roles in Development
During testis development, ptc1 and ptc2 are expressed in distinct cell
types, suggesting that these two proteins mediate separate aspects of
Dhh signaling. Dhh is the only Hh family member expressed in the
developing testis and is found in the Sertoli cells (Bitgood et al. 1996), a
cell type that supports the developing spermatogonia (Griswold 1995).
Targeted deletion of Dhh results in normal females but sterile males,
indicating that Dhh is critical for spermatogenesis (Bitgood et al. 1996).
In normal mice, ptc1 is expressed in the Leydig cells, which secrete
androgens and neighbor the Sertoli cells (de Kretser et al. 1998). In the
testes of Dhh deficient males, ptc1 expression is no longer detected in
the Leydig cells, presumably because Sertoli-derived Dhh is absent.
While this suggests Dhh mediates a signal from Sertoli to Leydig cells,
the Leydig cells in Dhh deficient males appear normal. The purpose of
this signaling event and the role of Ptc1 in testicular development is not
yet evident.
In contrast, ptc2 may have a critical role in spermatogenesis. In
normal mice, the high levels of ptc2 in the primary and secondary
spermatocytes suggest that Sertoli-derived Dhh also signals to the developing sperm (Carpenter et al. 1998). Consistent with this idea, a mouse
homolog ofJused (ju), a cytosolic component ofHh signaling in Drosophila, is expressed in the primary and secondary spermatocytes along
with ptc2 (Carpenter et al. 1998). This indicates that spermatocytes are
competent to respond to the Dhh. While it is not known how ptc2
expression is affected in Dhh deficient males, the above evidence argues
for a role of ptc2 in regulating Dhh signaling during spermatogenesis.
In the hair follicle, as in the testis, ptc1, and ptc2 have distinct
patterns of expression. Shh is expressed in the epithelial cell layer of the
developing hair follicle whereas ptc1 is found in the surrounding mesenchyme (Motoyama et al. 1998). These expression patterns imply that
Shh signals from the epithelia to adjacent mesenchymal cells. In contrast, ptc2 is detected in the same epithelial cells that express Shh
(Carpenter et al. 1998; Motoyama et al. 1998; Motoyama et al. 1998).
Motoyama et al. 1998). There are, however, two interesting exceptions,
the developing testes and hair follicle.
12.2.3 ptc1 and ptc2 May Have Separate Roles in Development
During testis development, ptc1 and ptc2 are expressed in distinct cell
types, suggesting that these two proteins mediate separate aspects of
Dhh signaling. Dhh is the only Hh family member expressed in the
developing testis and is found in the Sertoli cells (Bitgood et al. 1996), a
cell type that supports the developing spermatogonia (Griswold 1995).
Targeted deletion of Dhh results in normal females but sterile males,
indicating that Dhh is critical for spermatogenesis (Bitgood et al. 1996).
In normal mice, ptc1 is expressed in the Leydig cells, which secrete
androgens and neighbor the Sertoli cells (de Kretser et al. 1998). In the
testes of Dhh deficient males, ptc1 expression is no longer detected in
the Leydig cells, presumably because Sertoli-derived Dhh is absent.
While this suggests Dhh mediates a signal from Sertoli to Leydig cells,
the Leydig cells in Dhh deficient males appear normal. The purpose of
this signaling event and the role of Ptc1 in testicular development is not
yet evident.
In contrast, ptc2 may have a critical role in spermatogenesis. In
normal mice, the high levels of ptc2 in the primary and secondary
spermatocytes suggest that Sertoli-derived Dhh also signals to the developing sperm (Carpenter et al. 1998). Consistent with this idea, a mouse
homolog ofJused (ju), a cytosolic component ofHh signaling in Drosophila, is expressed in the primary and secondary spermatocytes along
with ptc2 (Carpenter et al. 1998). This indicates that spermatocytes are
competent to respond to the Dhh. While it is not known how ptc2
expression is affected in Dhh deficient males, the above evidence argues
for a role of ptc2 in regulating Dhh signaling during spermatogenesis.
In the hair follicle, as in the testis, ptc1, and ptc2 have distinct
patterns of expression. Shh is expressed in the epithelial cell layer of the
developing hair follicle whereas ptc1 is found in the surrounding mesenchyme (Motoyama et al. 1998). These expression patterns imply that
Shh signals from the epithelia to adjacent mesenchymal cells. In contrast, ptc2 is detected in the same epithelial cells that express Shh
(Carpenter et al. 1998; Motoyama et al. 1998; Motoyama et al. 1998).