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Frog development examples

How do you build a frog from a single cell? Learn how body axes are established and nerve tissue is induced in frog embryos.

Key points

  • The African clawed frog, Xenopus laevis, is a popular model organism studied by many developmental biologists.
  • The egg cell of a Xenopus frog is prepatterned by the mother frog with mstart text, R, N, A, end texts and proteins distributed unevenly between its two halves.
  • Body axes begin to form when the sperm enters the egg, setting up the dorsal-ventral—back-belly—axis and a region called the gray crescent.
  • The gray crescent turns into Spemann's organizer, a signaling center that "talks" with other tissues to direct development. Transplantation of an extra organizer into a newt embryo results in two newts joined at the belly!
  • Signaling by Spemann's organizer is a classic example of induction, a process through which one tissue sends signals to change the development of another.

Introduction

When you were younger, did you ever grow frogs in an aquarium? I have vivid memories of watching tadpoles hatch and metamorphose into adults, a process I found simultaneously kind of gross and totally amazing.
Actually, I still feel that combo of reactions about a lot of developmental biology—whether frogs are involved or not! In development, many experiments involve dissecting, injecting, analyzing, or otherwise manipulating very tiny bits of developing tissue with results that are sometimes pretty bizarre—like a two-headed newt or a frog that develops as a blob of mystery cells.
However, these experiments are the only way we can discover the intricate networks of genes that program the development of living things. In a series of cascading, largely self-organizing events, these networks coordinate and carry out the development of a complex organism from a single cell. From a more practical standpoint, development is often closely linked to disease—for instance, human cancer cells turn many early developmental genes back on.start superscript, 1, end superscript
As mentioned in the intro to development article, the embryonic development of just about any organism involves processes like cell division, establishment of axes—such as the head-to-tail axis—tissue and organ formation, and cell differentiation. In this article, we'll see examples of these processes in frogs, though probably not the kind of frogs you'd have grown in a tank as a kid!

Xenopus: our friend the African clawed frog

To make the processes of development a little more concrete, let’s consider an example: our friend the frog. To be more exact, let’s use a frog that’s a favorite of developmental biologists: Xenopus laevis, or the African clawed frog. This bizarre-looking name is pronounced ZEN-oh-puss LAY-vis.
Image credit: Xenopus laevis by Brian Gratwicke, CC BY 2.0
Xenopus has a relatively typical life cycle for a frog. A female frog lays eggs in the water, which are fertilized by sperm from a male frog. The resulting zygote goes through embryonic development to become a free-living tadpole, which then metamorphoses into an adult frog—for instance, by losing its tail through programmed cell death, or apoptosis.
Image credit: based on similar diagram from Xenbasesquared
Since Xenopus embryos develop outside of the mother frog's body, their development is much easier to watch than, say, the embryonic development of a mammal.squared In fact, I remember one of my professors telling us that you could squeeze a female Xenopus frog "like a tube of toothpaste" to get the eggs out for experiments! The eggs can be artificially fertilized with sperm from a male Xenopus, and scientists can watch as they develop in a dish.
Let's look at a few selected parts of Xenopus embryo development to see how they illustrate some of the basic processes of development.

Cell division and axis formation

In frogs, the egg cell is a massive cell—much larger than a normal frog cell—and it has an uneven distribution of various molecules, which are deposited in the egg by the mother frog before fertilization.start superscript, 3, comma, 4, end superscript This asymmetry is even visible in the egg: it has a dark-colored top—called the animal pole—and a light, yolky bottom—called the vegetal pole. Many mstart text, R, N, A, end texts and proteins from the mother frog are distributed unevenly between the animal and vegetal poles.
The key cue that kicks off embryonic development is the entry of the sperm into the egg, which can occur anywhere on the dark-colored upper portion, or animal pole.start superscript, 5, end superscript Of course, the sperm provides its genome, which alone makes it key to development! However, the sperm also acts as a positional signal that sets up a new axis in the embryo—the dorsal-ventral, or back-to-belly, axis.start superscript, 5, end superscript
How does this work? When the sperm enters the egg, the cytoplasm at the edge of the egg cell, called the cortical cytoplasm, rotates 30 degrees towards the site of sperm entry.start superscript, 5, end superscript Rotation exposes a wedge of the cytoplasm underneath, sometimes producing a visible zone of lighter color called the gray crescent.start superscript, 6, end superscript
The gray crescent corresponds to the future dorsal, or back, side of the embryo, while the the sperm entry site corresponds to the ventral, or belly, side.
Image credit: based on similar diagrams from Gilbertstart superscript, 5, end superscript and Stavelystart superscript, 7, end superscript
What does the rotation of the cytoplasm actually do to establish this axis? The basic idea is that molecules specifying dorsal, or back, fate—which are initially located in the cortical cytoplasm of the yolky bottom part of the egg—get shifted upwards, towards the animal pole of the zygote.start superscript, 8, end superscript There, they are placed in contact with other molecular factors—different from those in the cytoplasm near the vegetal pole—triggering events that lead to dorsal fate.
At this point, we're still looking at one big zygote. So, where do these cells we're talking about come from? An early Xenopus embryo is pretty much a cell division machine. Through many repeated rounds of cell division, the zygote—with its unequally distributed mstart text, R, N, A, end texts and proteins from the mother, including those shifted during cortical rotation—gets chopped up into many, many smaller cells. Cells in different regions of the embryo inherit different mstart text, R, N, A, end texts and proteins, which allow them to take on different identities and behaviors.start superscript, 4, end superscript
Image credits: upper diagram based on similar diagram in Gilbertcubed; lower photograph modified from Figure 3A: The phenotype of Foxi2-depleted (Foxi2 KO7) embryos by Cha et al.start superscript, 9, end superscript, CC BY 4.0

Making tissues and organs

How does our friend the frog go from a ball of cells to something that looks more like, well, a frog? The tadpole that forms in embryogenesis is the result of a huge number of genes being expressed in specific patterns and of their protein products interacting in different ways to set up yet other patterns of gene expression. A frog embryo is an amazing, self-organizing system, in which one molecular event triggers another in a cascade in time and space.start superscript, 10, end superscript
Understanding all of those events would be the work of a lifetime—so we're not going to attempt it in this article! In fact, even the best developmental biologists are pretty far away from understanding how a frog develops in full, Technicolor molecular detail. However, we can see one classic example of cascading events in development by looking at the behavior of cells in a particular area of the embryo—the area that develops from the gray crescent.

Case study: Spemann-Mangold organizer

What happens to the gray crescent we saw in the zygote? Let's trace where the cytoplasm from this area ends up in two later stages: blastula and gastrula.
The blastula is a ball of cells with a hollow space in the middle. In it, the gray crescent cells are found in a group on one side of the embryo, the dorsal side. This is pretty much where the gray crescent was in the zygote.
At the gastrula stage, however, these cells do something more interesting: they start marching into the interior of the embryo, causing the tissue to fold inward. The site where the cells migrate into the interior of the embryo is called the blastopore, and the gray crescent cells make up its dorsal lip.
Image credit: based on similar diagrams in Kimballstart superscript, 11, end superscript
What is the purpose of all this complex cell migration? For one thing, it's key to forming multiple layers of tissue in the embryo. But it's not just a matter of creating more layers; it's also a matter of cells in different tissues "talking" with one another and, in some cases, changing each other's fate. For instance, we now know that the cells that migrate inward instruct the cells above them, a type of tissue called ectoderm, to develop into neural—nervous system—tissue.
Image credit: based on similar diagram in Myersstart superscript, 12, end superscript
This interaction was first discovered in the 1920s by Hans Spemann and Hilde Mangold, in what is now one of the most classic experiments in embryology. Spemann and Mangold took the dorsal blastopore lip from a light-colored newt embryo and transplanted it into the belly, or ventral, side of a dark-colored newt embryo. This was a very technically demanding experiment, and Mangold worked for years to get five embryos in which it worked correctly!start superscript, 13, end superscript
Normally, the tissue at the transplant site would have turned into skin on the newt's belly, the ventral side. However, when the chunk of dorsal blastopore lip was transplanted in, its cells migrated inward, creating a second, functional gastrulation site opposite to the normal one.start superscript, 14, end superscript A new neural plate—the precursor of the spinal cord and brain—appeared at this second gastrulation site. In the end, an entire second newt formed from the belly of the original!
Image credit: based on similar diagrams in Gilbertstart superscript, 14, end superscript and Kimballstart superscript, 15, end superscript
What exactly happened in this experiment? There were two basic possibilities for how the transplanted tissue could have led to the formation of the second newt:
  • The transplanted tissue might have developed into the second newt all by itself, building its structures from the small group of transplanted cells.
  • The transplanted tissue might have "talked" to the layers of recipient tissue around it, organizing their behavior so that they—along with the transplanted cells—coordinated to form a second newt.
Thanks to the use of different-colored newts as donor and recipient, Mangold and Spemann were able to tell which possibility was correct. The structures found in the second newt's body consisted of some donor—light—cells but mostly recipient—dark—cells, meaning that cells in the transplanted tissue must have “talked” with the recipient cells nearby and induced them to change their behavior.start superscript, 16, end superscript This is a classic example of induction, in which a cell or tissue communicates with neighboring cells or tissues to alter their development.
Today, the cells of the dorsal blastopore lip and their descendants are called the Spemann-Mangold organizer. Two of the organizer's key roles are to specify dorsal—back, rather than belly—fate and to make nearby ectoderm turn into neural tissue. However, the organizer also guides head-tail axis development and other processes.start superscript, 14, end superscript
Importantly, the organizer itself doesn't directly guide the development of the entire newt. That is, it doesn't pull the strings, so to speak, that make each neuron in the newt's brain or photoreceptor in the newt's eye develop. Instead, it starts a chain reaction of molecular induction events that lead, domino-like, to the formation of the many complex structures of the newt's body—or, in the case of a transplant, to a second newt body!start superscript, 14, end superscript
The organizer acts largely by releasing secreted proteins that diffuse into the surrounding tissues and affect their behavior. For instance, some of the proteins released by the organizer bind to and neutralize other secreted proteins, which instruct cells to develop as skin. By interfering with the “Develop as skin!” cues, the organizer signals allow the overlying tissue to develop as neural tissue, actually its default path.start superscript, 10, comma, 15, end superscript

Want to join the conversation?

  • leaf green style avatar for user Alexander Wu
    Which part is the archenteron or coelom?
    (3 votes)
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    • blobby green style avatar for user wallacejoe
      This response is a few years late, but for those wondering... In late gastrula of figure. 6?, the archenteron is the space that forms from the blastopore lip. In blastula, you can see the blastocoel as the cavity at the top, it disappears shortly after the archenteron is formed.
      (2 votes)
  • hopper jumping style avatar for user Yago
    How is the uneven distribution of the molecules in the egg kept like that? Wouldn't the molecules tend to spread out evenly, even if they were positioned on one side of the cell in the beginning?
    (1 vote)
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    • blobby green style avatar for user skillfreak
      What I recall, in fruit flies, all the chemicals are locked on one side of the egg, and unlocked/released by molecules provided by sperm at time of fertilization. Once unlocked, the chemicals diffuse producing a gradient. Overtime, the chemicals will be uniformly distributed like you mentioned, and no longer be useful as location marker.
      (2 votes)
  • male robot hal style avatar for user RYAN DAVIS
    is there a part where I can disect a frog
    (1 vote)
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  • scuttlebug green style avatar for user Tzviofen ✡
    did this experiment have to be with light and dark embryos, or could it be that the only reason Hans Spemann and Hilde Mangold did that was to check at the end of the experiment if those cells really did use induction?
    (1 vote)
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  • blobby green style avatar for user Gianina Sophia  Cordova
    Which organ is developed first in the frog embryo?
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  • duskpin ultimate style avatar for user Pip
    "In fact, I remember one of my professors telling us that you could squeeze a female Xenopus frog "like a tube of toothpaste" to get the eggs out for experiments!"

    Wouldn't that hurt the frog? Or do scientists not care about that if they need something for their experiments? I'm sorry about how blunt this sounds, but I am vegan and a strong believer in animal rights, and was just wondering if some scientists use more humane methods to get what they need for their research.
    (0 votes)
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    • duskpin ultimate style avatar for user TerBur
      I agree and am curious as well, as to the humaneness of the methods used. I believe that all living beings should be treated the most humane way possible. Are there ethics guidelines regarding the use of animals in research? What do these guidelines entail?
      (1 vote)