The Embryonic Blueprint: Two Neural Systems Pushed Together
The brain is an immeasurably complex organ, and we’re only just scratching the surface of how it even comes into existence. New research published in Nature Neuroscience reveals that the brains of humans and other animals are actually made up of two collaborating neural systems that start developing in parallel in an embryo’s earliest moments. A Stanford-led research team discovered that the human brain did not always exist as a single distinct organ in human evolutionary history. On the contrary, it existed as two separate neural systems in space before moving together.
The researchers believe that the human brain came into existence as one after merging two separate neural systems. This discovery challenges a prevailing model of brain development as the scientists believed that a single progenitor cell gives rise to the entire brain. In reality, it consists of two ancient nervous systems packaged together. The study suggests that the different brain regions arise from separate kinds of embryonic cells known as progenitors. They found one progenitor cell type leads to the development of the forebrain and midbrain, while another goes on a totally different path to form the hindbrain. The scientists made their initial discovery by analyzing the way mouse brains developed from the very early embryonic stage known as gastrulation. Then, they confirmed that human pluripotent stem cells also follow these same paths, depending on the signals they receive.

Human pluripotent stem cells were differentiated into either anterior (aNE) or posterior (pNE) neural ectoderm-like cells within 2 days. pNE was fluorescently labeled, and then aNE (uncolored) and pNE (dye-labeled) were mixed. Co-cultures were treated with either forebrain-, midbrain-, or hindbrain-inducing signals for two additional days, before immunostaining. In a scientific first, they successfully encouraged the human stem cells to develop into hindbrain motor neurons, complete with electrical activity and proteins characteristic of these cells.
Researchers have identified two distinct, mutually exclusive populations of brain progenitor cells with strictly segregated developmental fates. The progenitor cells that create the fore- and midbrain regions produce a specific protein using a gene called Otx2, while the soon-to-be hindbrain cells express a gene called Gbx2. Both kinds of progenitor cells form the basis for the complete organ that is our brain, but their roles are not interchangeable. The way their DNA is packaged is fundamentally different too, with totally distinct chromatin ‘landscapes’. As Kyle Loh, developmental biologist, stated: “We’ve shown for the first time that the front of the brain arises from a totally different progenitor cell than the back of the brain.” Kyle Loh also noted: “Our discovery means that we can now grow neurons from the back of the brain, the hindbrain, in a Petri dish and study their functions.” As Kyle Loh further summarized: “Our research suggests that evolution took two existing neural systems and pushed them together spatially.” These findings could solve the mystery related to difficulty in growing certain types of brain cells in the lab along with opening new avenues for studying diseases.
Challenging Traditional Evolutionary Frameworks
Published in Science Advances, separate research draws on comparisons of biological brains and experiments on artificial neural networks to suggest a new framework for understanding the evolution of intelligence. For decades, the human brain was like some evolutionary skyscraper: ancient instincts on the bottom, emotions in the middle, and sophisticated reasoning on the top. That’s a good reason why we sometimes feel stuck between impulse and logic. But the evolutionary story of the brain may be far messier. New research from Georgia Tech challenges the popular notion of a primitive “lizard brain” sitting below a newer, rational brain. Instead, scientists suggest, it may have been a competition between fundamentally different ways of wiring neural circuits, with limited brain space forcing different systems to compete, which influenced brain evolution.

The old model was devised in the 1950s and perceived the brain in evolutionary layers, with basic bodily functions at the bottom, followed by an emotion-driven reptilian brain and finally the complex neocortex associated with human reasoning. But researchers now say this view is overly simplistic. The neocortex is involved in functions including vision, perception and reasoning. The so-called limbic system, often loosely described as the “reptilian brain,” is much more complicated. Its components play a role in memory, smell, navigation and emotional regulation and other functions. Rather than looking at the regions as separate structures, the Georgia Tech team examined how those regions change together across species through a concerted evolutionary change. They discovered that if one part of the limbic system was relatively large, then other parts of the limbic system were likely to be larger as well.
Rewriting the Human Family Tree
While developmental biologists re-examine brain origins, new research from Monash University suggests that recent discoveries about human evolution are challenging the traditional system scientists use to name and classify our ancestors. The research, published in the American Journal of Biological Anthropology, calls for a major reconsideration of human taxonomy. It proposes placing all human species and closely related fossil relatives from the past 4-5 million years within the genus Homo. Human evolution is often depicted as a relatively simple sequence of distinct species, beginning with ape-like ancestors, continuing through Australopithecus and early members of Homo, and eventually leading to Homo Sapiens living today. However, the fossil record reveals a much more complicated evolutionary history. As new fossils are discovered, many of the features once used to clearly separate humans from their close relatives have become increasingly difficult to define.

Lead researcher Dr. Ian Towle, a Research Fellow at the Monash Biomedicine Discovery Institute, said recent findings are making the existing classification system less useful and less accurate. That includes the way scientists categorize species within Homo as well as Australopithecus and Paranthropus, all of which lived during the past 5 million years. As Dr. Ian Towle stated: “Recent fossil discoveries and advances in evolutionary and genetic analysis make this an ideal time to reconsider whether our traditional taxonomy still accurately reflects human evolution.” Dr. Ian Towle also noted: “These groups do not necessarily represent distinct evolutionary branches, or ‘clades’, and differences in behavior and ecology once used to distinguish them have also become increasingly difficult to maintain.” Dr. Ian Towle further concluded: “I propose expanding Homo to include these other groups to provide a more accurate and stable way to represent the complex evolutionary relationships revealed by the growing fossil record.”