Regulation of Cell Polarity and RNA Localization in Vertebrate Oocytes - International Review of Cell and Molecular Biology - page 160

generalized axis defects, consistent with a disruption in the timing of Smad2
regulation ( Birsoy et al., 2006 ). Vertebrate Gdf1 has been implicated as a
cofactor in the long-range action of Nodal, but a similar role for maternal
Gdf1 in frog embryos has not been tested ( Tanaka et al., 2007 ). Additionally,
recent studies have shown a low level of activated Smad2 is present prior
to MBT, likely regulated by weak transcription of nodal-related 5/6 genes
also occurring before major zygotic transcription ( Skirkanich et al., 2011 ).
These require Vegt and beta-catenin for their expression ( Hyde and
Old, 2000; Xanthos et al., 2002 ), but it is possible that maternal Gdf1 has
a role as well.

4.2. Primordial germ cell specification
4.2.1 dazl
The Dazl family of proteins are widely involved in germ cell development in
both vertebrates and invertebrates, and defects in Dazl function are impli-
cated in human infertility ( Pan et al., 2009 ). Depletion of maternal dazl tran-
scripts in Xenopus resulted in defects in PGC formation and migration,
although early germ plasm structure and localization were unaffected
( Houston and King, 2000a ). PGCs in dazl -depleted embryos appeared to
form initially, but failed to disperse properly, showing increased clustering
in the gut. These PGCs also had defective migration toward the dorsal endo-
derm, suggesting a role for Dazl in regulating migrational competence in the
forming germline. However, a lack of zygotically expressed PGC markers
makes it difficult to assess the state of PGC specification in these cells. By
the late tailbud stages, dazl -depleted PGCs are lost either by apoptosis or
by differentiation into somatic cells ( Houston and King, 2000a ).
At the molecular level, Dazl has been implicated as positive regulator of
translation, potentially by binding to poly(A)-binding proteins during
translation initiation ( Collier et al., 2005; Pan et al., 2009 ). Additionally,
Dazl forms a complex on RNA with Pum2 protein ( Fox et al., 2005 ), a
known translational repressor, suggesting that Dazl may have dual roles in
both activating germline genes and repressing somatic cell genes in

the PGCs.
Interestingly, a phenotype similar to dazl depletion was seen in embryos
injected with an MO against dnd1 ( Horvay et al., 2006 ), suggesting these
two RNA-binding proteins might regulate similar pathways. Work from
zebrafish has suggested that Dnd1 binds to target mRNAs in the germline
and protects them from regulation by miRNAs ( Kedde et al., 2007 ).