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poly(A)polymerase TUTase4 (terminal uridylyltransferase 4), thus inhibiting
further processing of
pre-let-7
by Dicer (
Heo
et al
., 2008
). Consistently,
LIN-28 was found to be a crucial component in mouse PGC development,
as inhibition of LIN-28 function in PGCs resulted in loss of PRDM1
expression and failure to establish the germline. Together, LIN-28 can
relieve
Prdm1
from miRNA-mediated repression by abrogating
let-7
matu-
ration steps, allowing sustained expression of PRDM1 and proper germline
development (
West
et al
., 2009
). These results show that control over the
biogenesis of miRNAs can serve in regulating germline development.
2.3. miRNAs in germ cell maintenance and development
Following their arrival at the gonad, the germ cells associate with somatic
cells that support the maintenance of GSCs and regulate their differentiation
into the gametes (
Fig. 4.1
A(c) and C(b)). Different factors regulating GSC
self-renewal and maturation and the role of miRNA function in these
processes are discussed below.
2.3.1. miRNA function in maintenance and maturation
steps of GSCs
As miRNAs are essential for embryonic development (
Bernstein
et al
.,
2003; Giraldez
et al
., 2005; Grishok
et al
., 2001
), studying their role in the
GSC requires analysis of animals in which the function of Dicer is elimi-
nated specifically in these cells. Such experiments, conducted in
Drosophila
,
revealed a role for miRNAs in controlling GSC division. Here, miRNAs
were found to be crucial for the GSCs to pass the G1/S checkpoint, by
repressing the cell cycle inhibitor Dacapo (Dap). Similar to the defects in
dicer-1
females, GSCs of male flies show delay in the cell cycle at G1/S
transition (
Hatfield
et al
., 2005
). A more recent study suggests that Dap
repression mediated by the miRNAs miR-7, miR-278, and miR-309
depends on Insulin receptor signaling, thus providing an example for
cooperation between extrinsic and intrinsic signals in regulating GSC
division (
Yu
et al
., 2009
).
In addition to the role in controlling GSC division, the function of
Dicer-1 was found to be critical for maintaining the population of self-
renewing, nondifferentiated GSCs
(Jin and Xie, 2007)
. Similar defects in
GSCmaintenance were observed in flies carrying mutations in genes encod-
ing for different components of the miRNA pathway including the dsRNA-
binding protein Loquacious (Loqs), Ago1, and dFMRP (fragile X mental
retardation protein) (
Forstemann
et al
., 2005; Neumuller
et al
., 2008; Park
et al
., 2007; Pek
et al
., 2009; Yang
et al
., 2007a,b
). For example, the function
of the RNA-binding protein dFMRP, a component of miRISC that specif-
ically associates with the
bantam
miRNA, is important for the ability of
somatic stem cells (SSCs) of the ovary to support self-renewal of the GSCs
