Small RNAs in Germ Cell Development - Current Topics in Developmental Biology - page 89

( Yang et al ., 2007b, 2009 ). Conversely, differentiation of GSCs can be
achieved by inhibiting miRNA function as is the case for Maelstrom
(Mael), a protein that was originally identified as a PIWI-associated nuage
component in mouse ( Findley et al ., 2003; Soper et al ., 2008 ). Mael represses
miR-7 transcription, thereby allowing proper translation level of the Bag-
of-Marbles (Bam) protein, a crucial initiator of gametogenesis ( Pek et al .,
2009 ). Similarly, the Vasa protein, that is essential for proper germline
development, was shown to act by inhibiting miRNA function through its
binding to mei-P26 mRNA. In this case, the positive effect of Vasa on Mei-
P26 protein levels results in negative regulation of Ago1 function thereby
repressing the miRNA pathway ( Liu et al ., 2009; Neumuller et al ., 2008 ).
Together, in this context, miRNAs are important for promoting GSC
divisions and the maintenance of their pluripotent state, while repressing
premature differentiation of the cells into gametes. Therefore, the proper
differentiation of germline cells depends on mechanisms that would inhibit
miRNA function.
2.3.2. miRNA function in germ cell differentiation—Oogenesis
In contrast to the role of miRNAs in repressing GSC differentiation, further
studies in D. melanogaster revealed that the highly conserved miRNA-184 is
expressed in the female germline where it promotes multiple differentiation
steps during oogenesis and early embryogenesis. miR-184 regulates GSC
differentiation by tuning the levels of the Saxophone (Sax) receptor, which
responds to Dpp signals secreted from the niche cells, leading to suppression
of Bam ( Iovino et al ., 2009; Xie and Spradling, 1998 ). Thus, miR-184-
mediated repression of Sax leads to dampening of the Dpp signal resulting
in higher levels of Bam, thereby promoting GSC differentiation. Addition-
ally, miR-184 has an impact on oocyte and embryo dorsoventral and
anteroposterior polarity regulating the transport of the ventralizing signal
Gurken and the transcriptional repressor Tramtrack69, respectively ( Iovino
et al ., 2009 ).
Whereas Dicer function appears to be crucial for germline development
in some species, it is dispensable in the case of zebrafish where germline cells
lacking dicer give rise to eggs and sperm ( Giraldez et al ., 2005 ). The apparent
dispensability of Dicer-dependent small RNAs for zebrafish germline devel-
opment, however, still lacks an explanation.
2.3.3. miRNA function in germ cell
differentiation—Spermatogenesis
Genome-wide miRNA profiling revealed the presence of miRNAs in
mouse testis ( Barad et al ., 2004; Liu et al ., 2004a ), and that a number of
these are differentially expressed during spermatogenesis. Indeed, crucial
components of the miRNA machinery such as Dicer, AGO1, Drosha, and
testis-expressed miRNAs were found to be localized to the chromatoid