First published online December 20, 2005
Development 133, 205e (2006)
© The Company of Biologists Limited
GDF3: an early and conserved player in embryogenesis
Two papers in this issue focus on the role of growth differentiation factor
3 (GDF3) in early embryonic development. Mammalian GDF3 - which belongs to the
bone morphogenetic protein (BMP) branch of the TGFß superfamily - shares
considerable amino acid similarity with Xenopus Vg1. By studying the
role of GDF3 in early mouse patterning, Chen et al. (see
p. 319) have found that
Vg1 activity is remarkably well conserved. In Xenopus, Vg1 is
essential for early patterning and signals through a Nodal-like pathway (see
Development 133, 15-20). Here, the authors report that
Gdf3-null mouse mutants resemble mice with absent or reduced Nodal
signalling. Moreover, they report that GDF3 can interact with Nodal
co-receptors and antagonists. Nodal signalling is crucial for the formation
and positioning of the anterior visceral endoderm (AVE), which patterns the
anteroposterior axis of the embryo. The researchers found that 
30% of
Gdf3 null mutants have an abnormally formed or positioned AVE, and
they conclude that, like Vg1, GDF3 is required for Nodal pathway activity and
for proper axial patterning in the early
embryo.
In an accompanying paper (see
p. 209), GDF3 and Nodal
are reported to have even earlier roles in development than hitherto realised.
By exploring the role of GDF3 in embryonic stem (ES) cells, Levine and
Brivanlou have found that while higher GDF3 expression maintains pluripotency
in human ES cells, it is lower GDF3 expression that maintains pluripotency in
mouse ES cells. This apparent contradiction is consistent with their finding
that GDF3 directly inhibits BMP4. BMPs, which are necessary for cell fate
decisions in the blastocyst, promote human ES cell differentiation but
maintain mouse ES cells in an undifferentiated state. The authors discuss
several potential mechanisms - such as different sensitivities to BMP
signalling - for these species-specific responses.
Related articles in Development:
- GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos
- Ariel J. Levine and Ali H. Brivanlou
Development 2006 133: 209-216.
[Abstract]
[Full Text]
- The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo
- Canhe Chen, Stephanie M. Ware, Akira Sato, Dianne E. Houston-Hawkins, Raymond Habas, Martin M. Matzuk, Michael M. Shen, and Chester W. Brown
Development 2006 133: 319-329.
[Abstract]
[Full Text]
