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growth factors, can repopulate the testis of recipient mice and subse-
quently produce healthy offspring following intracytoplasmic sperm injec-
tion (
Ohinata et al., 2009
). More recently, a similar strategy has been utilized
to induce PGCs from embryonic stem (ES) cells (
Hayashi, Ohta, Kurimoto,
Aramaki, & Saitou, 2011
).
As of yet the role of BMPs in PGC specification has not been confirmed
in any other mammalian species although BMP4 may play a conserved role
in axolotl PGC induction (
Johnson et al., 2003
).
2.2. Specification genes
Initial attempts to uncover genes required for mouse PGC specification uti-
lized a single-cell differential expression screen between PGCs and somatic
neighboring cells isolated at E7.0-E7.5 (
Saitou, Barton, & Surani, 2002
).
Two differentially expressed genes
Fragilis
(
Ifitm3
) and
Stella
(
Pgc7
,
Dppa3
)
were characterized further and both exhibited expression patterns consistent
with a role in germ-cell specification. However, knockout mice for
Fragilis
are fertile, as are mice with a deletion of the entire
Ifitm
locus encompassing
Fragilis
1-5 (
Lange et al., 2008
). Similarly,
Stella
knockout mice exhibit no
gross PGC defects and are fertile (
Payer et al., 2003
), although
Stella
does
seem to play a role in the protection of maternal imprints in the zygote
(
Nakamura et al., 2007, 2012
). Nevertheless,
Stella
remains a useful marker
gene and transgenic reporter mice have proved valuable tools for isolating
and tracking PGCs (
Ohinata, Sano, Shigeta, Yamanaka, & Saitou, 2008;
Payer et al., 2006; West et al., 2009
). Further screening of differentially
expressed genes led to the discovery of a new candidate—
Blimp1
(
Prdm1
).
Blimp1
knockout leads to an early and profound loss of PGCs
(
Ohinata et al., 2005; Vincent et al., 2005
). A small cluster of less than 20
weakly staining Stella- and AP-positive cells can be found at the base of
the allantois in
Blimp1
null embryos at the 2-10 somite stage. However,
these cells do not appear to migrate appropriately from this position, and
after this stage, no more than one or two PGC-like cells can be detected
(
Ohinata et al., 2005; Vincent et al., 2005
). In contrast to wild-type PGCs,
these nascent PGC-like cells fail to repress expression of
Hoxa1
or
Hoxb1
by
the mid-bud stage (
Kurimoto et al., 2008; Ohinata et al., 2005
). This has led
to the hypothesis that a principal role of Blimp1 during PGC specification is
to repress the somatic program. This suggestion is consistent with Blimp1's
known function as a transcriptional repressor (
Keller & Maniatis, 1991
) and
subsequent global gene expression profiling of
Blimp1
null PGCs (
Kurimoto
