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Home | Pregnancy Timeline | News Alerts | News Archive June 13, 2013

Mouse embryo
Isl1 gene acts as a stop signal to axial progenitor genes

(A) During trunk to tail transition in a normal embryo, Isl1 is
activated exclusively in the progenitor cells that produce organs.
Progenitor cells now cannot make organs and progress to making legs.

(B) If there is a failure in the regulation of Isl1 activation and it is extended to the progenitor cells that form the spine, the spinal cells receive a stop signal and disappear without a trace.

Now the embryo cannot make more vertebrae and malformations are produced ,
which look similar to those observed in patients with spinal segmental disgenesis.

Credit: Moisés Mallo, Instituto Gulbenkian de Ciência (IGC), Portugal.

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How to make a tail? The leg is key!

A new study reveals how the trunk of a body transitions into a tail in vertebrates.

One of the most remarkable anatomical differences among vertebrate body shape is the relative size of a vertbrate's neck, trunk and tail. Compare the bodies of a typical snake and a long tailed lizard. They are both very long and superficially similar. However, most of the snake's body is a trunk filled with digestive, excretory and reproductive organs. Whereas, the largest part of the lizard's body is a muscular tail. These different body plans are genetically determined during embryonic development.

In the latest issue of the journal Developmental Cell, Moisés Mallo and his group at the Instituto Gulbenkian de Ciência (IGC), Portugal, showed that the trunk to tail transition is intrinsically associated with the induction of the legs and the embryonic cloaca, and that this process is coordinated by a genetic cascade triggered by the signaling factor Gdf11. This study may contribute to understand some congenital human syndromes that lead to malformations in the lower part of the body.

During embryonic development, the body forms progressively with cell growth starting from the head and progressing through to the tail. This process depends on the activity of a group of cells known as axial progenitors, which are located at the posterior tip of the embryo and produce new tissues while extending.

After the head and neck are made, these progenitors engage in making the trunk of the body, including most of the animal's vital organs. At a particular signal, the embryonic growth program changes and starts producing tail tissues instead of trunk tissues.

This change occurs at the same time as the embryo forms the cloaca—the opening end of all three digestive, reproductive and urinary tracts, and the legs (or hindlimbs).

Moisés Mallo and his team found that the production of the cloaca and the legs is an intrinsic component of the trunk to tail transition and have identified several key regulators of this process. The most significant being that Gdf11 signaling is at the top of the genetic hierarchy regulating the trunk to tail transition.

Moisés Mallo's team found that if Gdf11 is genetically inactivated in the mouse, the animals have longer trunks and their legs are located further away from their arms (or forelimbs) than in normal mice.

When in the complementary experiment they forced the premature activation of Gdf11, the result was just the opposite: extremely reduced trunks and the hindlimbs located just next to the forelimbs.

"Our jaws almost touched the floor when we first saw those embryos because such strong alterations in the leg position have never been observed before" said Moisés Mallo.

These researchers also identified some of the key pieces involved in the execution of the program initiated by Gdf11 that ends the trunk and starts the tail.

One of the most interesting of those pieces is the gene Isl1 (Islet 1). Gdf11 activates this gene specifically in the subgroup of axial progenitors responsible for making the internal organs in the trunk.

The consequence of Isl1 activation is that these progenitors are now forced to form cloaca and hindlimbs instead of organs. This indicates that the vertebrate legs are actually the consequence of the way Isl1 manages to stop this group of progenitors from making internal organs when they are no longer required.

Mallo's work also revealed that the genetic program regulating trunk to tail transition must be perfectly coordinated in time. Any alteration leads to a wide spectrum of malformations in the lower end of the body, typically affecting the vertebral column and the gastrointestinal, reproductive and urinary tracts.

These malformations closely reproduce the clinical characteristics of human pathologies such as the caudal regression syndrome or the spinal segmental dysgenesis, indicating that they might originate from alterations in the trunk to tail transition during embryonic development.

Moisés Mallo says: "What we found might be important not only to understand the mechanisms that generate the wide anatomical diversity among vertebrate species, but might also provide important clues to understand some of these congenital human syndromes"

This study was carried out at the IGC and was funded by Fundação para a Ciência e a Tecnologia (Portugal).

*Jurberg, A.D., Aires, R. Varela-Lasheras, I., Nóvoa, A., Mallo, M. (2013) Switching Axial Progenitors from Producing Trunk to Tail Tissues in Vertebrate Embryos, Dev. Cell.(http://dx.doi.org/10.1016/j.devcel.2013.05.009)

Original press release: http://www.igc.gulbenkian.pt/pages/article.php/A=279___collection=pressReleases___year=2013