Biology Reference
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body, a germ cell specific structure where RNA-processing takes place
(
Gonzalez-Gonzalez
et al
., 2008; Kotaja
et al
., 2006
). Consistently, reducing
the function of Dicer in mouse PGCs resulted in germ cell proliferation
defects and aberrant differentiation of spermatogonia manifested by
abnormal spermatids morphology and sperms with impaired motility
(
Hayashi
et al
., 2008; Maatouk
et al
., 2008
). Whereas these phenotypes
could also reflect roles for endo-siRNAs in spermatogenesis since both rely
on Dicer, the function of miRNAs was demonstrated in this context. An
interesting observation was that despite the global meiotic transcriptional
silencing of genes located on the X chromosome, many X-linked miRNAs
escape this inhibition and are transcribed in spermatocytes during meiosis
(
Song
et al
., 2009
). Specific roles for miRNAs in spermatogenesis were
assigned, for example, to the miR-17-92 cluster that was shown to repress
the translation of the transcription factor E2F1, thereby protecting meiotic
cells from apoptosis (
Novotny
et al
., 2007
). Similarly, Mirn122a was sug-
gested to be predominantly expressed in late stage male germ cells, where it
represses specific RNAs expressed in spermatogenesis (
Yu
et al
., 2005
).
2.3.4. miRNA function in sex differentiation
The involvement of miRNAs in sex-specific PGC differentiation was sug-
gested by analysis of expression profiles of mouse PGCs at E9.5-E13.5. In these
studies, differential expression ofmiRNAswas detectedwhen comparingmale
and female PGCs. While the functional importance of the differences in
expression should be further investigated, differential expression was detected
for
let-7
, miR-125a, miR-9, and miR-29b (
Hayashi
et al
., 2008; Takada
et al
.,
2009
). Indeed, repression of
dnmt3a
and
dnmt3b
(
de novo
methyl transferases 3a
and b, respectively) by the female-biased expressed miR-29b allows the GSCs
to escape the genome-wide methylation observed in males at E15 (
Lees-
Murdock
et al
., 2005
). Together, these findings provide initial hints concerning
the possible function miRNAs play in sex determination and differentiation.
2.4. miRNA function in the somatic cells of the gonad
Proper development of GSC depends on signals provided by surrounding
gonadal somatic cells that in turn regulate cell division, self-renewal, and
differentiation. Regulation of gene expression in those somatic cells by
miRNAs thus influences GSC maintenance and differentiation processes.
2.4.1. miRNAs in gonadal somatic cells support germ
cell development
As described above, depletion of
dicer-1
in
Drosophila
GSC leads to failure of
GSC maintenance as a result of defects in cell cycle and self-renewal
(
Hatfield
et al
., 2005; Jin and Xie, 2007
). In addition, removing the function
