The Moving Cells that Make Our Pups the Pups They Are Today

What makes dogs so doggy? You might have noticed that your dog has traits, like floppy ears, a curly tail, speckles or patches, or a cute, short nose,  that make it look pretty different from the wolf it’s descended from. For more than a century, scientists have wondered why so many domesticated animals, ranging from cows to pigs to mice, share traits like these that don’t exist in the wild animals they’re related to.

Now researchers think they’ve solved the mystery, and it comes from an unexpected place: a group of traveling cells that grow deep inside the brain before journeying across the growing embryo and developing into an adult animal. It turns out that this small group of cells, moving around long before the animal is even born, is critical for development of all kinds of traits. Not only are these cells vitally important for domestication, but they even play important roles in human health—we need them for important parts of the body, like the brain and heart, to be able to grow.

My dog Clover’s floppy ears and white patches are adorable – but why are they there? Photo courtesy of Leah Wallach.

In 1868, Darwin first noticed and described the group of unexpected traits that appear when we breed animals to live with us, calling it “domestication syndrome.” When later scientists tried to solve the puzzle of how changes in the body and brain make animals friendly to humans, domestication syndrome seemed like a key part of the problem.

For years, scientists struggled to identify what genes controlled these traits. They could tell which parts of the brain had changed to make animals less fearful. They could also, by comparing domesticated and wild animals, find some of the genes that, in different parts of the body, seemed to be working differently. But they struggled to put it all into a clear picture.

Then, a group of scientists, led by Dr. W. T. Fitch at the University of Vienna, realized that they’d been looking in the wrong place. It didn’t seem possible for the genes they studied to cause so many changes in different parts of the body. Instead, they found that the domestication-linked genes change a single group of cells, called the neural crest (NC) cells. These cells spread through the body of the developing embryo, leading to the different, seemingly unrelated features of domestication syndrome.

How Neural Crest Cells Move through the Body

At first, NC cells grow along with the rest of the tissues in the embryo, in a sheet of cells called the neural epithelium. These cells are all destined to become part of the nervous system: the brain, spinal cord, and nerves. However, unlike the rest of the neural epithelium cells, the NC cells have a very unusual way of growing: they pop out of the surrounding sheet of cells then journey through the body, where they help form important body parts ranging from the pigment in skin to the tubes and valves of the heart.

Many other traveling cells, like red blood cells, have special guides and channels that keep them on the right track in the body. NC cells don’t have that physical guide, however. Instead, chemical signals are released by different parts of the body that help NC cells know exactly where to go. NC cells can sense how strong a signal is and they move toward the area where a particular signal is strongest.

Once they know where to go, NC cells form a cluster and start making a structural protein called actin. The cells arrange the actin in a ring around the outside of the cluster like a belt to hold it together. You might remember actin from high school as the protein involved in allowing our muscles to contract. Likewise, the actin ring surrounding the NC cell cluster can expand and contract. When the NC cells detect the signal they are meant to follow, the back of the actin ring contracts. This propels the cells forward allowing them to move, independent of any other part of the body, toward their new home.

The face, ears, skin, brain, and spine are among the body parts that NC cells help to produce. (Adapted from Wilkins et al.)

Genes that change NC Cell Movement Lead to Domestication Syndrome

Once scientists determined that all the domesticated traits could be attributed to changes in the NC cells, new questions arose. Were genes changing the destination of NC cells? How did these NC cells develop once they got to where they were going?

What the Fitch group suspected, and later studies have supported, is that the genes that were changed with domestication were the genes dictating the chemical signals that tell the NC cells where to go. Small alterations to these signals change how far the cells go and where they land when they’re ready to develop into a new part of the body. When breeders select to breed dogs with more docile characteristics, they are essentially choosing to pass on genes that affect the animal’s brain. However, because NC cells spread throughout the body and not just the brain, this gene selection leads to extra, unexpected results.

One theory is that the NC cells of domesticated animals don’t move as far as NC cells of wild animals. For instance, some NC cells form cartilage in the ears and tail. The failure to spread cartilage all the way out to the tips of these body parts could possibly lead to floppy ears or a curly tail. Similarly, if NC cells that make pigment don’t spread as far as normal, it could be the reason why white patches or speckles often show up in domesticated animals.

All of this helps us understand what, exactly, happens when NC cells build the body. Not only does that give us a better understanding of our furry friends and how to take care of them, it can help us understand how NC cell movements might even affect human health, too. When NC cells don’t know where to go while a human embryo is developing, it can cause problems in how different parts of the body develop. This can sometimes cause serious health conditions, and even deadly birth defects.

Understanding how these NC cells move and how their movement changes due to mutations in animals like dogs or mice can ultimately help us understand how these processes work in humans. This research is essential to unlocking solutions for how to fix and prevent birth defects that are caused by defective NC cell movement. NC cells are key to vital processes throughout the body– studying NC cells improves our health and helps us understand what makes a dog a dog.

Leah Wallach is a fourth-year undergraduate student at the University of Chicago, studying biology and writing. Her research focuses on embryonic development and cell division. She is also active in science education and outreach for Chicago-area high school students. She can be found on LinkedIn and Twitter.

Leah Wallach’s article is part of a collaboration between the Illinois Science Council and the University of Chicago.