Regulation of Cell Polarity and RNA Localization in Vertebrate Oocytes - International Review of Cell and Molecular Biology - page 159

4.1. Germ layer induction and patterning
4.1.1 vegt
The mRNA for vegt , encoding a maternal T-domain transcription factor,
was initially isolated simultaneously by several groups ( Lustig et al., 1996;
Stennard et al., 1996; Zhang and King, 1996 ). Transcripts were localized
throughout the vegetal cortical hemisphere in a manner similar to gdf1 .
Endoderm forms predominantly from vegetal cells, and overexpression
experiments showed that Vegt induces both endoderm and mesoderm
( Lustig et al., 1996; Stennard et al., 1996; Zhang and King, 1996 ). Impor-
tantly, depletion of maternal vegt mRNA led to loss of the endoderm
markers in vegetal cells and also indirectly to loss of mesoderm. The
mesoderm-inducing activity of vegetal explants in Nieuwkoop rec-
ombinants was lost when vegt was depleted, suggesting that Vegt activated
transcription of the mesoderm-inducing growth factors ( Zhang et al.,
1998 ). Subsequent experiments verified these as members of the Nodal
family of TGF-beta family of proteins ( Agius et al., 2000; Kofron et al.,
1999 ). Vegt is thus critical for the formation of two of the three primary
germ layers. Similarly, in zebrafish, a related T-box encoding mRNA, eomes ,
is required maternally for endoderm formation, as is pou5f1 ( Bruce et al.,
2003; Lunde et al., 2004; Reim et al., 2004 ).
4.1.2 gdf1
Although gdf1 was the first localized mRNA identified, the extent of its
involvement in embryonic patterning in development remained un-
certain. Gdf1 was initially thought to be a candidate for the vegetal
mesoderm-inducing factor, and Gdf1 engineered to be efficiently processed,
indeed, had potent activity in embryos ( Thomsen and Melton, 1993 ). How-
ever, many other TGF-beta molecules had mesoderm-inducing activity
( Asashima et al., 1990; Jones et al., 1992; Smith et al., 1990 ). It also became
evident that mesoderm induction occurred primarily after ZGA at the
midblastula stage ( Wylie et al., 1996 ). This and the discovery of the activa-
tion of Nodal expression by Vegt left the role of maternal Gdf1 mysterious.
A reinvestigation of gdf1 function using oligo-mediated maternal
mRNA depletion showed that Gdf1 may be involved in initiating Smad2
phosphorylation in the late blastula ( Birsoy et al., 2006 ). Mesoderm induc-
tion and patterning depend critically on proper spatiotemporal regulation of
Smad2 across the dorsoventral axis, involving both positive and negative
feedback ( Faure et al., 2000; Whitman, 2001 ). Gdf1 -depleted embryos have