June 27, 2008 — More than 80 years have
passed since the German scientist Hans Spemann conducted his famous
experiment that laid the foundations for the field of embryonic
development. After dividing a salamander embryo in half, Spemann
noticed that one half — specifically, the half that gives rise to the
salamander’s ‘belly’ (ventral) starts to wither away.
However, the other ‘back’ (dorsal) half that develops into its head,
brain and spinal cord, continues to grow, regenerating the missing
belly half and develops into a complete, though be it smaller, fully
Spemann then conducted another experiment, where this time, he
removed a few cells from the back half of one embryo and transplanted
them into the belly half of a different embryo. To his surprise, this
gave rise to a Siamese twin embryo where an extra head was generated
from the transplanted cells. Moreover, although the resulting embryo
was smaller than normal, all its tissues and organs developed in the
right proportions irrespective of its size, and functioned properly.
For this work, Spemann received the Nobel Prize in Physiology or Medicine in 1935.
But how does this happen? How exactly is the half embryo able to
maintain its tissues and organs in the correct proportions despite
being smaller than a normal sized embryo?
Despite many years of research, this question has remained
unanswered — until now. More than 80 years since Spemann’s classic
experiment, Profs. Naama Barkai, Benny Shilo and research student Danny
Ben-Zvi of the Weizmann Institute of Science’s Molecular Genetics
Department, together with Prof. Abraham Fainsod of the Hebrew
University-Hadassah School of Medicine, Jerusalem, have finally
discovered the mechanisms involved.
Previous studies have shown that the growth and development of cells
and organs within the embryo is somehow linked to a special group of
substances called morphogens. These morphogens are produced in one
particular area within the embryo and then spread throughout the entire
embryo in varying concentrations. Scientists then began to realize that
the fate of embryo cells, that is to say, the type of tissue and organ
they are eventually going to develop into, is determined by the
concentration of morphogen that they come into contact with. But this
information does not answer the specific question as to how proportion
is maintained between organs?
The idea for the present research came about when Weizmann Institute
scientist Prof. Naama Barkai and her colleagues developed a
mathematical model to describe interactions that occur within genetic
networks of an embryo.
The data ascertained from this model suggest that the way morphogens
spread throughout the embryo in different concentrations is different
than previously thought. The team predicts that an inhibitor molecule,
which is secreted from a localized source at one side of the embryo and
can bind the morphogen, acts as a type of ferry that ‘shuttles’ the
morphogen to the other side. Therefore, the mathematical model suggests
that it is the interactions between the two substances that enable the
embryo to keep the relative proportion between organs constant,
irrespective of its size. Indeed, these predictions have been validated
by experiments conducted on frog embryos by the research team.
The importance of the role of these morphogenic substances, as well
as their mechanism of action, is evident by the fact that they have
been conserved throughout evolution, where different variants can be
found to exist in species ranging from worms to fruit flies and up to
higher species including humans. Therefore, understanding the processes
that govern embryonic cell development could have many implications.
For example, it may lead, in the future, to scientists being able to
repair injured tissues.
Prof. Naama Barkai’s research is supported by the Kahn Family
Foundation for Humanitarian Support; the Helen and Martin Kimmel Award
for Innovative Investigation; the Carolito Stiftung; the Minna James
Heineman Stiftung; the PW-Iris Foundation; and the PW-Jani. M Research
Prof. Benny Shilo’s research is supported by the Y. Leon Benoziyo
Institute for Molecular Medicine; the Dr. Josef Cohn Minerva Center for
Biomembrane Research; the J & R Center for Scientific Research; the
Jeanne and Joseph Nissim Foundation for Life Sciences Research; and the
Mary Ralph Designated Philanthropic Fund. Prof. Shilo is the incumbent
of the Hilda and Cecil Lewis Professorial Chair in Molecular Genetics.
Source : Weizmann Institute of Science