FREE Excerpt from BS 201 with Bill Harris:

I want to thank Dr. Harris again for coming on Brain Science to talk about his book Zero to Birth: How the Human Brain Is Built.

Brain development is a complicated subject, and this book is a great introduction to how we know what we currently know. It's not a beginner level book, but I recommend it to everyone working in other areas of neuroscience or medicine. Whether or not you choose to read this book, the goal of this review is to emphasize a few key ideas.

Before I talk about brain development, I want to highlight a few other points. One of the big themes that comes from this book is the idea of evolutionary continuity. We have so much in common with other life, even single-celled organisms. As Harris pointed out, even paramecia generate action potentials or voltage spikes, even though they use calcium channels instead of sodium.

They also use signaling proteins, the same ones that are neurotransmitters in our nervous system. I did mention Seth Grant because he was the first one who made me aware of this.

We also have continuity with invertebrates like fruit flies and our basic nervous system and our body plan is chaired with all vertebrates. How does this happen?

Well, every cell in our body contains the entire genome. So, it's which genes are actually turned on that matter. Some genes code for transcription factors that turn on other genes, and so they can have a much bigger impact especially if they turn on many other genes.

So, I want to start out by just reviewing the basic steps of brain formation, and I'm going to leave out most of the terminology to focus on the key ideas of what happens.

We start out as a ball of pluripotent cells that develops three layers that are going to become the main tissues of the body. The outer layer is called the ectoderm, and it will become skin or nervous tissue.

During a process called gastrulation, a section of the ectoderm called the neural plate gets pushed inside the embryo or pushed inside the ball and eventually, forms the neural tube, which is what will become the brain and the spinal cord. This happens in all vertebrates.

Once this basic plan has been established, the neural stem cells divide into a combination of stem cells and neurons, so that at birth, we have most of the neurons we will ever have.

The brain continues to grow after birth due the growth of both connections and glial cells. Once the neurons have formed, they have to begin to make connections. This is a process that continues after birth and obviously, throughout life. Finally, the neurons begin to send action potentials to each other and to tissues like muscles.

It's kind of ironic that once the synapses are formed, the neurons actually have to compete for survival. I want to go through this again so that you can get it solid in your head.

The pluripotent cells become part of the ectoderm and then the neuroectoderm, which is what will become the nervous system. During gastrulation, a structure called the neural plate is pushed inside the embryo and becomes the neural tube. The brain and spinal cord develop from the neural tube. Once this basic structure’s in place, the neural stem cells begin to become neurons.

The neurons send out axons to connect to other neurons or tissues such as muscles. Some neurons actually die before birth because they don't form successful synapses or because they have been part of a scaffold for building the brain and are no longer needed.

We actually have the most neurons we will ever have before we are born, and at the time we are born, we will get very few additional neurons because neurons cannot divide or reproduce. Glial cells and synapses will continue to form.

Obviously, brain development is extremely complex and during our conversation, we barely touch on some of the fascinating discoveries about how it works. If you're interested in learning more, I highly recommend this book Zero to Birth: How the Human Brain Is Built by William A. Harris.

We did explore a few key questions, like how does the basic body plan, including the brain and the spinal cord, come about. And since there are thousands of types of neurons, what determines the identity of any particular neuron, and how do the axons reach the right target.

Harris mentioned just a few of the scientists who have worked on these questions, going back to the early days of embryology, before we had the complex tools of molecular biology that now, allow actual manipulation of genes to see what will happen.

One of my favorite parts of this book is the descriptions of some of the groundbreaking experiments that have been done, some under extremely challenging conditions.

Another cool thing is the surprises that have occurred along the way. For example, for years, it was assumed that neuro stem cells needed a particular signal to become neurons.

But as Harris mentioned, it actually turns out that the ectodermal cells will become neurons unless they get a signal that tells them to become skin cells. Sort of like the way a fetus will be a female if it doesn't get the signals to make male sex organs.

Another surprise we touched on during our conversation was the recent evidence that rather than evolving many times in the past, the key components of vision may have a common origin that goes back to the genes for photosensitive proteins in bacteria.

Harris mentioned the experiment that showed that the human PAX6 gene can be inserted into a genetically blind fly and its compound eyes will form normally. That seems almost unbelievable given how different human eyes are from the compound eyes of flies.

Even though this is a podcast about neuroscience, I think it is important to have a basic understanding of how the tools of molecular biology and genetics are integral, not just to neuroscience, but to every life science.

What does it mean to say that we share much of our genetic makeup with other animals like fruit flies and single-celled organisms like bacteria? The key is remembering what genes actually do. They code for making proteins and proteins can have a huge variety of functions. Some become parts of complex structures, but others are transcription factors, which means that they turn other genes on or off.

Some of these transcription factors seem to turn on whole cascades of other genes. This means that they might have similar but different functions in different animals. An example of this, is the hox family of genes, that's spelled H-O-X.

We talked a little bit about the hox family of genes which are arranged in sequence that corresponds to the head-to-toe structures of the body. They were first discovered in fruit flies, and a scientist named Ed Harris showed that if the hox genes were inserted into other cells, it was possible to grow extra wings or extra legs where they wouldn't normally be located.

However, Bill Harris emphasized that these hox genes don't code for chemical signals. They actually code for proteins that are transcription factors that may turn on thousands of other genes.

Unless you work in this field, it's not necessary to worry about the details. I picked the hox gene as an example because it is one of the ones that is found in invertebrates like fruit flies, but they only have one set of eight hox genes while vertebrates have four sets. This is because the sets were apparently duplicated twice during early vertebrate evolution.

I first learned about this gene duplication, which I think occurred about 250 million years ago from Seth Grant, and I think it is a very under-appreciated element of why vertebrates were able to evolve into more complex and diverse species.

I want to close by mentioning a point that Harris emphasized near the end of the interview; at birth, each baby's brain is unique. It's not a blank slate.

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