In Simple Terms
Scientists mapped how deep brain cells develop before and after birth, using data from nearly 287,000 cells. Some mature early, while others keep developing after birth. The map also links certain cells’ genetic patterns to signals associated with schizophrenia and bipolar disorder, but it does not show that those cells cause either condition.
Why the Basal Ganglia Are Hard to Trace
Deep inside the brain, circuits involved in movement, habits and responses to rewards take shape over a long journey that begins before birth. During this process, nerve cells are produced in temporary regions, then move to their final destinations as the activity of their genes changes and they mature. A new study in Cell offers a detailed map of this process in the human basal ganglia and connects some of its genetic features with inherited signals associated with psychiatric disorders.
The basal ganglia are a collection of structures deep within the brain, not a single isolated cluster. Their circuits help regulate movement, form habits, process rewards and shape some aspects of behavior. Disruptions in their function are associated with a range of conditions, from Parkinson’s and Huntington’s diseases to addiction, obsessive-compulsive disorder and schizophrenia. But understanding what these circuits do in adults does not, by itself, explain how they were built in the developing brain.
Some of the nerve cells associated with this region arise in embryonic structures called ganglionic eminences. These structures temporarily produce neurons, then change and disappear as development proceeds; they do not persist in the same form after birth. That makes it difficult to reconstruct their history by examining an adult brain: the cells’ original source is gone, and the cells themselves have already undergone substantial development and migration.
Pinpointing a cell’s location or identifying the genes active within it is only part of the challenge. Gene activity is also shaped by chemical regulation that affects how accessible genes are, as well as by the way genetic material is arranged inside the nucleus. The genetic instructions may be present, but the folding of DNA and the chemical marks around it help determine when those instructions can be read in a particular cell.
Looking Beyond Gene Activity
To investigate these layers of regulation, the team used a technique called single-nucleus methyl-3C sequencing, or snm3C-seq. It captures two kinds of information at once: DNA methylation patterns, which are chemical marks associated with gene regulation, and the way sections of chromatin—the material made up of DNA and its associated proteins—make contact in three dimensions inside the nucleus.
Combining these measurements matters because simply counting the genes active in a cell does not reveal the full system controlling them. Mapping how genetic material folds adds information about which regions come close together inside the nucleus, while methylation provides clues about regulatory signals. Together, these measurements offer a broader view of the changes that accompany a cell’s shift from an early state to a more mature one, rather than just a snapshot of gene activity.
The researchers analyzed more than 155,000 cell nuclei from nine developing human brains. The samples covered stages from mid-gestation through the period after birth, up to seven months of age. When the new data were combined with earlier datasets from different developmental stages and adult brains, the resulting atlas contained nearly 287,000 cells.
The study did not rely on a single measurement. The team combined sequencing data with spatial analysis of gene expression and imaging of individual chromatin and RNA molecules. These complementary methods help connect a cell’s features with its location and developmental stage, adding detail about how growth is organized in the ganglionic eminences and in the cells that develop from them.
Not Every Cell Matures on the Same Schedule
The map showed that cell groups originating in different subregions of the ganglionic eminences do not follow a single developmental timetable. Some neuronal lineages had reached a degree of molecular maturity by mid-gestation, while other groups of precursor cells continued producing immature neurons into infancy.
This difference matters for understanding brain development: it cannot be treated as a process in which every cell advances at the same pace. Each cell type follows its own path, and steps that occur together in one group may take longer in another. Comparing these paths gives researchers a way to identify what distinguishes each lineage, when its defining features emerge, and how it changes as it leaves its birthplace or settles into its target circuits.
One cell type that stood out was the medium spiny neuron, a major type of neuron that sends signals out of parts of the basal ganglia. The data showed that these neurons undergo a more coordinated maturation process than nearby neuronal types, with molecular signs associated with functional activity appearing as early as mid-gestation. These features suggest that the formation of their circuits begins early—before birth—not only during childhood.
The findings also showed that these cells do not acquire their final identities all at once. Instead, their subtypes emerge alongside coordinated changes in the three-dimensional organization of the genome. By contrast, the maturation of other cell types appeared less synchronized. This comparison allows researchers to view the timing of regulatory changes as part of a cell’s identity, rather than as a background process that simply runs alongside its development.
A Temporary Reorganization After Birth
The researchers also examined oligodendrocytes, support cells that mature and produce myelin, a sheath around nerve fibers. Myelin helps insulate the fibers and regulate the transmission of signals along them. As immature precursor cells developed into cells capable of making myelin, the atlas revealed a temporary pattern of short-range chromatin organization during infancy.
This transient organization was associated with increased gene transcription—the production of RNA copies of genetic information for use in the cell. The observation shows that the way genetic material is folded need not remain fixed throughout a cell’s life. A particular pattern may appear during a transitional stage and then change as the cell differentiates. This adds to our understanding of how support cells change as neural circuits continue developing after birth.
This finding is important because descriptions of cells often focus on the starting point and the endpoint: a precursor cell, then a mature cell. Detecting a temporary chromatin state reveals an intermediate stage that may have its own regulatory activity. The atlas therefore offers a more dynamic picture of development, in which the organization of genetic material inside the nucleus can change along the way rather than serving only as a final feature.
Where Do Genetic Risk Signals Appear?
After building the atlas, the researchers compared the cells’ features with data from genome-wide association studies, or GWAS. These studies look for genetic differences that occur at varying frequencies across large groups and may be statistically associated with a higher likelihood of a particular condition. But finding an association in a region of the genome does not automatically reveal which cells are affected or when in life that association may matter.
When the researchers compared the two datasets, they found a notable concentration of schizophrenia-associated genetic variants in developing medium spiny neurons. Some subtypes of these cells also showed significant associations with variants linked to bipolar disorder. The atlas is valuable because it places genetic signals in the context of specific cells and a developmental pathway that extends from fetal life into the period after birth.
These findings do not mean that medium spiny neurons cause schizophrenia or bipolar disorder. The study examined tissue from typically developing brains, not samples from people with these conditions, and a genetic association alone does not establish a causal mechanism. Instead, the results narrow the field of inquiry: researchers can ask more precisely which cells and stages of circuit formation may be relevant to how inherited susceptibility influences risk.
Recognizing these limits helps prevent the findings from being overstated. The atlas is not a test for predicting who will develop a psychiatric disorder, nor does it show that a particular change occurs in every person who carries a genetic variant associated with risk. It is a research reference for comparing typical development with observations from disease models or future studies, and it may help identify molecular features that warrant direct investigation.
A Research Collaboration and a Reference Map
The work was led by researchers at the University of California, Los Angeles; the University of California, San Francisco; and the University of California, San Diego, as part of the Brain Initiative Cell Atlas Network (BICAN), associated with the U.S. National Institutes of Health’s Brain Initiative. The scientific leads included Chongyuan Luo and Jason Ernst of UCLA, Mercedes Paredes of UCSF, and Eran Mukamel of UCSD.
The study was published in Cell on November 12, 2026, under a title describing the creation of a multimodal, cell-level atlas of human basal ganglia development. It was funded by the National Institutes of Health, with additional support from the Chan Zuckerberg Initiative. The scale of the collaboration reflects the size of the task: collecting samples from different ages, applying multiple technologies and organizing the results into a reference that other researchers can use for comparison.
The reference is useful because it brings together three questions: What kind of cell is present? What is changing in the organization of its genetic material? And when during development does that change happen? Answering all three is more informative than simply listing active genes, especially when cells originate in a temporary structure and later move elsewhere. The atlas can also help researchers compare typical development with the results of future experiments, without assuming that every genetic association means disease is inevitable.
The Bottom Line
The basal ganglia atlas offers a detailed picture of the different paths taken by nerve cells and support cells from mid-gestation through infancy. Drawing on data from nearly 287,000 cells, it shows that some mature early while other groups continue producing immature cells after birth. Medium spiny neurons stood out for their coordinated, early maturation and for genetic signals associated with schizophrenia and, in some subtypes, bipolar disorder.
The findings do not settle the origins of psychiatric disorders or prove a cause-and-effect relationship. They do give future research a more precise starting point: particular cell types, developmental windows to investigate and changes in genome organization to compare. In a brain region whose development cannot be understood by looking only at the adult brain, this map offers a window onto the stages when its circuits are first built.