Small RNAs in Germ Cell Development - Current Topics in Developmental Biology - page 91

of Dicer-1 in SSCs of the ovary revealed a function in this cell population as
well. Similar to the GSC, SSCs lacking Dicer-1 failed to self-renew leading
to their depletion in the niche and premature differentiation, resulting in
defects in follicle cell proliferation and growth (Jin and Xie, 2007) . Consis-
tently, mutants for loqs and ago1 affecting the miRNA pathway displayed
abnormally developed germaria ( Forstemann et al ., 2005; Park et al ., 2007;
Yang et al ., 2007a ). An example for a gene regulated by miRNAs in somatic
cells of the ovary is notch ( Deng et al ., 2001; Lopez-Schier and St Johnston,
2001 ). Here, Belle, a component of the miRNA pathway, was found to
regulate the timing of Notch activity in follicle cells. Loss of Belle delays
Notch activation thus delaying follicle differentiation that in turn affects
GSC cell cycle and maturation ( Poulton et al ., 2011 ).
A role for miRNAs in somatic gonadal cells was further demonstrated in
male mice, where the development of sertoli cells that tightly control
spermatogenesis depends on this level of regulation. Selective ablation of
dicer in these somatic cells results in impaired sertoli cell maturation that leads
to a complete absence of spermatozoa and progressive testicular degenera-
tion. Similarly, somatic cell development in the female mouse also relies on
miRNA-mediated regulation. In this case, somatic granulosa cells that
surround the developing oocyte and support its development appear to
require Dicer function. Specific depletion of dicer in granulosa cells leads
to degeneration of follicles in the mutant ovaries. This effect results from
premature onset of folliculogenesis caused by lack of mmu-miR-503,
which normally fine tunes the levels of Cyclin D2 (CCND2), an important
regulator of cell proliferation during folliculogenesis ( Lei et al ., 2010 ).
Moreover, dicer depletion in somatic cells of the gonad also affects the
development of somatic reproductive tissues, resulting in defects in ovula-
tion, oocyte migration from oviduct to uterus, and subsequent implantation
( Gonzalez and Behringer, 2009; Hong et al ., 2008; Nagaraja et al ., 2008 ).
Together, these results suggest that Dicer function is critical for sper-
matogenesis and for proper development of oviducts and uterus and plays a
role in regulating folliculogenesis by maintaining the communication
between germline and somatic cells in the gonad.
2.4.2. miRNAs and hormonal regulation of gametogenesis
During oogenesis and spermatogenesis, factors like the follicle stimulating
hormone (FSH), luteinizing hormone (LH) and steroid hormones (e.g.,
estrogen, progesterone, and androgen) are key regulatory factors ( Combelles
et al ., 2004; Dong et al ., 1996 ; reviewed in Edson et al ., 2009 ) and miR-132
and miR-212 were found to be important for the response to those hormone
signals ( Fiedler et al ., 2008 ). For example, LH triggers downstream cAMP
signaling events, which in turn can activate CREB (cAMP response element
binding), a repressor of miR-132 and miR-212 transcription in granulosa cells
( Fiedler et al ., 2008 ). Interestingly, the miRNA expression levels can in turn