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

Aug 02, 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: Researchers discover new strategy germs use to invade cells

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

add to favorites email to friend print save as pdf

Related Stories

New protein promotes embryonic brain formation

Dec 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 ...

When cells are consumed by wanderlust

Jul 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 ...

Recommended for you

Researchers discover new strategy germs use to invade cells

8 hours ago

The hospital germ Pseudomonas aeruginosa wraps itself into the membrane of human cells: A team led by Dr. Thorsten Eierhoff and Junior Professor Dr. Winfried Römer from the Institute of Biology II, members of the Cluster ...

Progress in the fight against harmful fungi

9 hours ago

A group of researchers at the Max F. Perutz Laboratories has created one of the three world's largest gene libraries for the Candida glabrata yeast, which is harmful to humans. Molecular analysis of the Candida ...

How steroid hormones enable plants to grow

Aug 19, 2014

Plants can adapt extremely quickly to changes in their environment. Hormones, chemical messengers that are activated in direct response to light and temperature stimuli help them achieve this. Plant steroid ...

Surviving the attack of killer microbes

Aug 19, 2014

The ability to find food and avoid predation dictates whether most organisms live to spread their genes to the next generation or die trying. But for some species of microbe, a unique virus changes the rules ...

Histones and the mystery of cell proliferation

Aug 19, 2014

Before cells divide, they create so much genetic material that it must be wound onto spools before the two new cells can split apart. These spools are actually proteins called histones, and they must multiply ...

User comments : 0