Biology Reference
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Besmer, & Bernstein, 1988; Geissler & Ryan, 1988; Huang et al., 1990;
Williams et al., 1990
). c-Kit is expressed in PGCs throughout their devel-
opment (
Manova & Bachvarova, 1991; Orr-Urtreger et al., 1990
), while SF
is expressed along the migratory pathway and in the genital ridges (
Matsui,
Zsebo, & Hogan, 1990
). SF is specifically downregulated in the midline
between E9.5 and E10.5, resulting in apoptosis of PGCs that have failed
to move laterally toward the genital ridges (
Runyan et al., 2006
). Thus,
the expression pattern of SF appears to define the boundaries for PGC
migration, although cell adhesion to laminins may also play a role
(
Garc
´
a-Castro, Anderson, Heasman, & Wylie, 1997
). Blocking PGC
apoptosis in
Steel
mutant embryos, by simultaneously knocking out
the proapoptotic gene
Bax
(
Knudson, Tung, Tourtellotte, Brown, &
Korsmeyer, 1995; Stallock & Wylie, 2003
), confirms that SF is required
for appropriate migration and reveals that SF also regulates PGC prolifera-
tion
in vivo
(
Runyan et al., 2006
). The migration of PGCs also requires
directionality. The initial movement away from the base of the allantois
may in part be due to morphogenetic tissue movement (
Mclaren, 2003
).
However, in the hindgut, PGCs are highly motile (
Molyneaux et al.,
2001
). They move first ventrally into the dorsal midline between
E9.0-9.5, before moving laterally to the genital ridges during the
E10-10.5 period (
Molyneaux et al., 2001
). The possibility that the genital
ridges release a chemoattractant molecule is supported by the observation
that PGCs actively migrate toward dissected genital ridges (
Godin, Wylie,
& Heasman, 1990
). In keeping with this, the ligand/receptor pair SDF1,
expressed by the genital ridge, and CXCR4, expressed by PGCs, are critical
players for colonization of the developing gonad (
Molyneaux et al., 2003
).
Very few of the PGCs found in the gut mesentery at E10.5 migrate into
the genital ridge (
Molyneaux et al., 2001
) and they most likely undergo
apoptosis (
Runyan et al., 2006
).
Upon reaching the genital ridges, PGCs commence expression of
Mvh
,
a specific germline marker until the postmeiotic stage in males and females
(
Toyooka et al., 2000
).
Dazl
and
Sycp3
exhibit a similar expression pattern
(
Cooke, Lee, Kerr, & Ruggiu, 1996; Di Carlo, Travia, & de Felici, 2000;
Osterlund, T
¨
h
¨
nen, Forslund, &Nordqvist, 2000
). All three genes are reg-
ulated by promoter DNA methylation (
Maatouk & Resnick, 2006
) with
their reexpression possibly reflecting global changes in DNA methylation
occurring at this time (see later). Indeed, recent evidence suggests that
many genes implicated in later stages of germ-cell development, such as
gametogenesis and meiosis, are regulated by promoter DNA methylation
