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of the germarium results in an increase in rate of GSC division and number
(
Cox
et al
., 1998; Szakmary
et al
., 2005
). Indeed, Piwi proteins are important
for gonadal and germline development as the function of both Piwi and Aub
is required for male and female fertility (
Cox
et al
., 1998; Lin and Spradling,
1997; Schmidt
et al
., 1999
); consistently Ago3 has been shown to be required
for female fertility as well, but only partially for male fertility (
Li
et al
., 2009
).
The three mouse PIWI proteins, MIWI, MILI, and MIWI-2, are
expressed during spermatogenesis in mitotically arrested prenatal GSCs
(
Aravin
et al
., 2008
), and consistent with the idea that they function in
these stages, both
mili
and
miwi-2
mutants exhibit spermatogenic stem cell
arrest defects and massive degeneration of spermatogonia observed in
miwi-
2
knockout mice (
Carmell
et al
., 2007; Unhavaithaya
et al
., 2009
). Germ cell
development in Zebrafish as well requires the Piwi proteins, Ziwi (zebrafish
PIWI) and Zili (zebrafish PIWI-like) (
Houwing
et al
., 2008, 2007
), as in
zebrafish
ziwi
mutants, germ cells undergo apoptosis, resulting in male
infertility, while in fish lacking
zili
, loss of germ cell differentiation to
mature oocytes or sperm is observed. A role for Piwi proteins in gameto-
genesis was also demonstrated in mice, where
miwi-2
mutants show pre-
dominant arrest at the Leptotene stage of meiosis (
Carmell
et al
., 2007
). The
mutant spermatogenic cells show defects in dsDNA break repair, which is
consistent with a role in proper meiotic recombination (
Carmell
et al
., 2007;
Kuramochi-Miyagawa
et al
., 2004
). Similarly, germ cells in mice lacking
MILI function are blocked at the zygotene or early pachytene stages of
meiotic prophase (
Kuramochi-Miyagawa
et al
., 2004
). Defects in meiosis
have also been observed in mutant flies for Piwi proteins and proteins
involved in repeat-associated siRNA (
Chen
et al
., 2007; Klattenhoff
et al
.,
2007; Lim and Kai, 2007; Pane
et al
., 2007
).
Last, a role for a piRNAs in spermatogenesis was demonstrated in
C. elegans
. In this case, the Piwi-like protein PRG-1 that is localized to
P-granules was shown to be required for successful spermatogenesis. Loss of
prg-1
leads to a strong reduction in the expression of 21U-RNAs during
spermatogenesis correlated with extensive defects in sperm activation and
fertilization (
Batista
et al
., 2008; Wang and Reinke, 2008
).
5. Conclusion
This review highlights the function of the different classes of small
RNAs in regulating specification and maintenance of the germline, as well
as the role in executing the function of this cell lineage, namely the
generation of sperm and egg. Given the importance of the germline in
propagation of the species, numerous functional redundancies can be iden-
tified in the control over germline development, contributing to the
