Biology Reference
In-Depth Information
reported that
Prdm14
null PGCs do not undergo some of the characteristic
epigenetic changes that occur in PGCs soon after specification (see
Section 4
). Tcfap2c/Ap-2
g
is expressed in PGCs from E7.25 and based
on expression profiling is a putative Blimp1 target (
Kurimoto et al., 2008;
Weber et al., 2010
).
Tcfap2c
knockout results in a loss of PGCs around
E8.0 (
Weber et al., 2010
). The authors found that PGCs generated from
Tcfap2c
null ES cells by an embryoid body differentiation protocol
had increased levels of some differentiation markers, including
Hoxa1
,
Hoxb1
, and
T
, and that
HOXA1
,
HOXB1
,
MYOD1
, and
HAND1
were
upregulated upon
TCFAP2C
knockdown in a human seminoma cell line.
Weber and colleagues conclude that Tcfap2c may function downstream of
Blimp1 to suppress mesodermal differentiation.
There is scant literature detailing gene expression changes during spec-
ification in other mammals. Blimp1 is expressed in rat PGCs by E8.5 (
Leitch
et al., 2010
), but its expression at earlier stages is not known. Due to limited
access to early stage human embryos, the gene expression pattern during
human PGCs specification, which occurs before the 4th week of develop-
ment, are largely unknown. However, LIN28 (
Childs, Kinnell, He, &
Anderson, 2012; Gillis et al., 2011
), BLIMP1 (
Eckert et al., 2008
) and
TCFAP2C (
Pauls et al., 2005
) are reported to be expressed in human
PGCs/gonocytes at around week 6 to 10 postconception (CS17 onward),
respectively. Given the importance of these factors in early mouse PGC
development, the expression of LIN28, BLIMP1, and TCFAP2C in human
PGCs may indicate conserved roles in PGC specification and maintenance.
2.3. Pluripotency-associated genes and specification
As previously noted, the entire network of pluripotency genes, with the
exception of
Klf4
, becomes specifically upregulated in nascent PGCs. Their
expression is relatively specific to the PGC period of germline development,
in general lasting until around the time of sex-specific differentiation.
Furthermore,
Oct4
and
Nanog
have been reported to be necessary for
PGC development (
Chambers et al., 2007; Kehler et al., 2004; Okamura,
Tokitake, Niwa, & Matsui, 2008; Yamaguchi et al., 2009
). However,
due to their requirement for preimplantation development (
Mitsui et al.,
2003; Nichols et al., 1998
), conditional approaches have been necessary
to assess their function in PGCs. Deletion of
Oct4
using
tissue non-specific alka-
line phosphatase
(
TNAP
)-cre leads to apoptotic death of most PGCs as they
colonize the gonads (
Kehler et al., 2004
). The few surviving germ cells are
