School of Medicine

How do developing brains assemble and organize themselves?

Linda Richards (at microscope), head of the Department of Neuroscience at Washington University School of Medicine in St. Louis, recently published a study describing some of the earliest events in brain development. The findings lay the groundwork for understanding the roots of brain conditions such as epilepsy, autism and intellectual disability. (Photo: Huy Mach/School of Medicine)

Babies are born with brains pre-organized into areas dedicated to movement, vision, hearing and other functions, a critical infrastructure that equips them to start learning about the world from the moment they take their first breaths. But little is known about how the brain’s architecture is built because of the challenges involved in studying brain development before birth.

Enter fat-tailed dunnarts, mouse-like marsupials that are born after just 13 days of gestation, with brains still largely unformed. By monitoring the brain development of dunnart joeys as they matured in their mothers’ pouches, researchers at Washington University School of Medicine in St. Louis gleaned insights into how the outer surface of the brain, known as the cortex, organizes and structures itself — a crucial process that has been all but impenetrable to scientific investigation up to now. Understanding how brain structure normally emerges could provide essential clues to why and how the process sometimes goes awry, leading to neurological disorders.

The study is available online in the journal Proceedings of the National Academy of Sciences.

“Even as the cortex is still forming, distinct patterns of activity emerge in different functional areas of the brain,” said senior author Linda J. Richards, PhD, the Edison Professor of Neurobiology and head of the Department of Neuroscience. “These patterns may be critical for establishing connections between different brain areas. We’d like to know how patterned activity develops across the brain and what happens when that goes wrong. How do alterations to patterned activity disrupt how brain circuits are set up, and what implications might that have for brain conditions such as epilepsy or autism?”

The development of the nervous system in mammals, including humans, starts with the emergence of a so-called neural tube in the first weeks after conception. One end of the neural tube buds into a brain; the other lengthens into the spinal cord. Over several weeks, cells in the outer surface of the nascent brain organize themselves into the cerebral cortex, the crumpled outer surface of the brain responsible for memory, thinking, learning, sensing and emotions. A dunnart is born just after the neural tube forms, so its cerebral cortex develops while it is in its mother’s pouch. In people, the cerebral cortex begins to form about five weeks after conception and continues developing into the second trimester of pregnancy.

Along with Richards, the research team included co-author Geoffrey J. Goodhill, PhD, a professor of developmental biology and of neuroscience at the School of Medicine; as well as co-first authors Rodrigo Suárez, Tobias Bluett and Michael H. McCullough, all of whom were at the University of Queensland in Australia when the initial research was conducted.

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