Active balance between two proteins ensures that embryos develop with the proper proportions

August 2, 2013
Figure 1: The ventral and dorsal ‘ends’ of a Xenopus embryo (top) are respectively defined by cells with high levels of Sizzled (top left) and Chordin (top right). This dorsal-ventral boundary can be shifted (bottom) by reducing levels of Chordin, leading to overproduction of Sizzled (bottom left), or reduced levels of Sizzled, which in turn leads to increased Chordin degradation (bottom right). Credit: 2013 Elsevier

Early in development, the embryo establishes the various axes that determine the symmetry of the mature animal. For example, the patterning of dorsal and ventral surfaces governs formation of the organism's back and belly. There are developmental mechanisms that regulate this patterning to ensure that the various body parts develop in proportion to each other but exactly how these mechanisms function remains uncertain. Yoshiki Sasai, Hidehiko Inomata and colleagues from the RIKEN Center for Developmental Biology have now clarified how dorsal-ventral (DV) scaling is maintained in the African clawed frog, Xenopus laevis.

A cluster of cells known as Spemann's organizer establishes the 'dorsality' of the embryo by secreting the protein Chordin, which inhibits signals that would otherwise initiate development of ventral tissues. The effect of Chordin is known to be tightly constrained to the dorsal region. "If a Xenopus embryo is bisected into a dorsal and ventral half, the dorsal half will still give rise to a well-proportioned, half-size embryo," explains Inomata. However, the mechanism responsible for localizing the effect of Chordin was previously unknown.

The researchers conducted a series of experiments to understand how Xenopus establishes this DV boundary. Chordin is naturally degraded by protease enzymes distributed throughout the early embryo. These are selectively inhibited by another protein called Sizzled, and the researchers found that Chordin's reach is determined by the range at which Sizzled can block protease activity.

Sizzled is primarily produced at the ventral pole of the embryo via the same 'ventralizing' signal that gets switched off by Chordin. This creates a critical : Chordin only acts in cells where Sizzled is present, but Sizzled is only produced in cells where Chordin levels are low. The DV boundary is thus established in those cells where Chordin prevents continued production of Sizzled and where low levels of Sizzled prevent further diffusion of Chordin (Fig. 1). Regardless of embryo size, this boundary reliably scales with the distance of the organizer from the ventral pole. "Our results indicate that the dynamic state of Sizzled protein accumulation conveys body size information for scaling," says Inomata.

While these findings resolve an important developmental puzzle, the frog embryo lacks important elements of complexity found in other vertebrate species. "During early Xenopus development, the size of the embryo is nearly unchanged, but in many animals the embryo becomes larger and dynamically changes size," says Inomata. "We'd like to examine whether our scaling model is applicable to this type of growing developmental field."

Explore further: New protein promotes embryonic brain formation

More information: Inomata, H., Shibata, T., Haraguchi, T. & Sasai, Y. Scaling of dorsal-ventral patterning by embryo size-dependent degradation of Spemann's organizer signals. Cell 153, 1296–1311 (2013). dx.doi.org/10.1016/j.cell.2013.05.004

Related Stories

New protein promotes embryonic brain formation

December 24, 2010

The various bone morphogenetic protein (BMP) signaling factors play an important role in early neural development in the vertebrate embryo. However, maturation of these tissues ultimately depends on the coordinated activity ...

Researchers revise long-held theory of fruit-fly development

December 17, 2009

For decades, science texts have told a simple and straightforward story about a particular protein—a transcription factor—that helps the embryo of the fruit fly, Drosophila melanogaster, pattern tissues in a manner that ...

When cells are consumed by wanderlust

July 22, 2013

(Medical Xpress)—In experiments on zebrafish, Freiburg researchers have demonstrated that the same proteins that lead to the formation of metastases in humans also cause the cells to migrate during embryonic development. ...

Recommended for you

How fungi helped create life as we know it

December 18, 2017

Today our world is visually dominated by animals and plants, but this world would not have been possible without fungi, say University of Leeds scientists.

Study answers a long-standing mystery about snake predation

December 18, 2017

Rattlesnakes experience the world very differently from humans. A specialized pit on the snake's face contains a heat-sensitive membrane which connects to the brain. Together, the snake's visual and heat-sensing systems work ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.