Several protein interactions help to establish the front and back sides of an embryo
An important stage in the early development of an embryo is the formation of the dorsal–ventral axis, which distinguishes the front (ventral) side of the animal from the back (dorsal). RIKEN researchers at the Center for Developmental Biology in Kobe are identifying the genes and proteins that contribute to this process in Xenopus laevis, the African clawed frog.
Before the dorsal–ventral axis becomes established, the embryo is essentially a symmetrical sphere. The first signs that the symmetry is broken are uneven distributions in a complex network of proteins called the Wnt signaling pathway. However the differences in Wnt activity are too small to induce such a dramatic polarization, implying that other factors may amplify the effect.
The researchers found that XTsh3, a protein produced by the so-called Teashirt (Tsh) gene family, was strongly expressed in dorsal areas of the embryo1. “In Xenopus, it is easy to see gene functions by RNA injection into embryos,” says team leader Yoshiki Sasai. “XTsh3 injection induced dorsalization of the embryos.” Furthermore, when XTsh3 activity was deliberately inhibited, the dorsal axis didn’t form at all (Fig. 1 - click on link below).
The activity of XTsh3 was found to be strongly related to levels of a protein called β-catenin, which has a crucial role in Wnt signaling. β-catenin accumulates in the cell nucleus and activates target genes that contribute further to the dorsal development.
“XTsh3 is an essential amplifier of Wnt signaling, which is activated on the dorsal side soon after insemination,” says Sasai. However the formation of the dorsal axis doesn’t occur until several hours later. In future Sasai would like to investigate the specific timings of each event. “One of our favorite hypotheses is that XTsh3 may be involved in the persisting memory of Wnt activation on the dorsal side.”
XTsh3 may have even more functions that the team has not yet discovered, because the molecule has the potential to bind with DNA. For example, the high levels of XTsh3 in the nervous system may contribute to development of the spinal cord once the dorsal–ventral axis is established.
Abnormal Wnt activation is also known to cause certain types of colon cancer in mammals. Four Tsh family genes are known in humans, but the roles of the genes are still to be investigated. It is also not known how far Tsh’s functions are conserved across species. Studies on the Drosophila fruit fly have shown a possible role of Tsh in Wnt signaling, but so far no link between Tsh activity and axis formation.
Reference
1. Onai, T., Matsuo-Takasaki, M., Inomata, H., Aramaki, T., Matsumura, M., Yakura, R., Sasai, N. & Sasai, Y. XTsh3 is an essential enhancing factor of canonical Wnt signaling in Xenopus axial determination. The EMBO Journal 26, 2350–2360 (2007).
