Signaling Components in Dorsal-Ventral
4 Patterning and the Organizer in Xenopus
Edward M. De Robertis and Nydia Tejeda-Muñoz
CONTENTS
4.1. Historical Background ................................................................................................................................................. 43
4.2. The Search for Spemann Organizer Molecules in Xenopus......................................................................................... 44
4.2.1. Goosecoid ....................................................................................................................................................... 44
4.3. The Ventral Signaling Center ....................................................................................................................................... 45
4.4. BMP Antagonists and Tissue Differentiation............................................................................................................... 45
4.5. Neural Induction by the Organizer............................................................................................................................... 47
4.6. The Chordin/Tolloid/Twisted Gastrulation/Crossveinless-2/BMP Ancestrally Conserved D-V Patterning System ... 47
4.7. Self-Regulation by Spemann Organizer Relocalization .............................................................................................. 47
4.8. Future Avenues of Research ......................................................................................................................................... 48
References .............................................................................................................................................................................. 49
“Les théories passent, la grenouille reste.”
“Theories pass, but the frog remains.”
Jean Rostand—Le carnet d’un biologiste—1959
4.1. HISTORICAL BACKGROUND
Watching a fertilized animal egg develop into an embryo
with many tissues is fascinating. How could something as
complex happen? Embryology became the forefront of biological research when researchers realized that rather than a
descriptive approach, experimental challenges were required
to unravel the mechanisms of development. The frog embryo
led the way. In 1883, Wilhelm Roux killed one of the two
blastomeres of a frog embryo with a hot needle and found that
the surviving cell gave rise to only a half embryo. However,
in 1891, Hans Driesch separated the frst two blastomeres of a
sea urchin embryo and found that each cell could self-organize
and give rise to a complete, albeit smaller, embryo (reviewed
in Spemann, 1938). The discordant results were clarif ed by
Thomas Hunt Morgan (who before becoming a geneticist was
an experimental embryologist), who repeated Roux’s experiment and found that if the dead blastomere were gently pipetted out of the frog embryo, frogs also could self-regulate and
generate a complete tadpole from half an egg (Morgan, 1895).
Using baby hair loops to slowly constrict newt eggs at the oneor two-cell stage, Hans Spemann later obtained twins from
the same amphibian egg (Spemann, 1938).
One can imagine that understanding the mechanisms
leading to making two out of one would be next to impossible.
Yet the way forward was pointed by an experiment carried out by a graduate student at Freiburg University, Hilde
Mangold. Under the direction of Spemann, who had found
that the dorsal lip of the blastopore was the frst region of
the embryo to become determined, she transplanted dorsal
lips into the ventral side of host embryos from newt species
that differed in their degree of pigmentation. In experiments
based largely on two embryos with secondary axes—no statistical signifcance analyses were required back then—she
described in wonderful camera lucida drawings of histological sections that the transplanted dorsal organizer gave
rise mostly to notochord, while the neighboring cells were
induced to form a Siamese twin containing dorsal tissues
such as somites and central nervous system. This was the
most famous experiment in embryology ( Spemann and
Mangold, 1924 ). Tragically, Hilde Mangold, who had a
small baby, died before her paper was published. Spemann
received the Nobel Prize for Physiology or Medicine in
1935 for the discovery of embryonic induction of histotypic
differentiation.
The Spemann-Mangold experiment marked the apogee of
experimental embryology. A furry of experiments attempted
to identify the chemical substance that was able to induce
the central nervous system (CNS), also called the primary
inducer. However, given the methods available at the time,
all efforts failed, and experimental embryology gradually faded ( Hurtado and De Robertis, 2007 ). The genetics
founded by Morgan with the use of the Drosophila fruit f y
became the pre-eminent biological discipline for most of the
20th century.
By the 1970s, it was common to hear famous professors say
that Spemann had set back developmental biology by 50 years.
Experimental embryology was forgotten. That all changed in
the 1990s, when molecular biology became practical and new
genes could be readily isolated. A wonderful memoir about
DOI: 10.1201/9781003050230-5
43
4 Patterning and the Organizer in Xenopus
Edward M. De Robertis and Nydia Tejeda-Muñoz
CONTENTS
4.1. Historical Background ................................................................................................................................................. 43
4.2. The Search for Spemann Organizer Molecules in Xenopus......................................................................................... 44
4.2.1. Goosecoid ....................................................................................................................................................... 44
4.3. The Ventral Signaling Center ....................................................................................................................................... 45
4.4. BMP Antagonists and Tissue Differentiation............................................................................................................... 45
4.5. Neural Induction by the Organizer............................................................................................................................... 47
4.6. The Chordin/Tolloid/Twisted Gastrulation/Crossveinless-2/BMP Ancestrally Conserved D-V Patterning System ... 47
4.7. Self-Regulation by Spemann Organizer Relocalization .............................................................................................. 47
4.8. Future Avenues of Research ......................................................................................................................................... 48
References .............................................................................................................................................................................. 49
“Les théories passent, la grenouille reste.”
“Theories pass, but the frog remains.”
Jean Rostand—Le carnet d’un biologiste—1959
4.1. HISTORICAL BACKGROUND
Watching a fertilized animal egg develop into an embryo
with many tissues is fascinating. How could something as
complex happen? Embryology became the forefront of biological research when researchers realized that rather than a
descriptive approach, experimental challenges were required
to unravel the mechanisms of development. The frog embryo
led the way. In 1883, Wilhelm Roux killed one of the two
blastomeres of a frog embryo with a hot needle and found that
the surviving cell gave rise to only a half embryo. However,
in 1891, Hans Driesch separated the frst two blastomeres of a
sea urchin embryo and found that each cell could self-organize
and give rise to a complete, albeit smaller, embryo (reviewed
in Spemann, 1938). The discordant results were clarif ed by
Thomas Hunt Morgan (who before becoming a geneticist was
an experimental embryologist), who repeated Roux’s experiment and found that if the dead blastomere were gently pipetted out of the frog embryo, frogs also could self-regulate and
generate a complete tadpole from half an egg (Morgan, 1895).
Using baby hair loops to slowly constrict newt eggs at the oneor two-cell stage, Hans Spemann later obtained twins from
the same amphibian egg (Spemann, 1938).
One can imagine that understanding the mechanisms
leading to making two out of one would be next to impossible.
Yet the way forward was pointed by an experiment carried out by a graduate student at Freiburg University, Hilde
Mangold. Under the direction of Spemann, who had found
that the dorsal lip of the blastopore was the frst region of
the embryo to become determined, she transplanted dorsal
lips into the ventral side of host embryos from newt species
that differed in their degree of pigmentation. In experiments
based largely on two embryos with secondary axes—no statistical signifcance analyses were required back then—she
described in wonderful camera lucida drawings of histological sections that the transplanted dorsal organizer gave
rise mostly to notochord, while the neighboring cells were
induced to form a Siamese twin containing dorsal tissues
such as somites and central nervous system. This was the
most famous experiment in embryology ( Spemann and
Mangold, 1924 ). Tragically, Hilde Mangold, who had a
small baby, died before her paper was published. Spemann
received the Nobel Prize for Physiology or Medicine in
1935 for the discovery of embryonic induction of histotypic
differentiation.
The Spemann-Mangold experiment marked the apogee of
experimental embryology. A furry of experiments attempted
to identify the chemical substance that was able to induce
the central nervous system (CNS), also called the primary
inducer. However, given the methods available at the time,
all efforts failed, and experimental embryology gradually faded ( Hurtado and De Robertis, 2007 ). The genetics
founded by Morgan with the use of the Drosophila fruit f y
became the pre-eminent biological discipline for most of the
20th century.
By the 1970s, it was common to hear famous professors say
that Spemann had set back developmental biology by 50 years.
Experimental embryology was forgotten. That all changed in
the 1990s, when molecular biology became practical and new
genes could be readily isolated. A wonderful memoir about
DOI: 10.1201/9781003050230-5
43