The hindbrain, which becomes the brainstem and cerebellum, is the first part of the brain to develop. It begins forming during weeks 3 and 4 of pregnancy, when the embryo’s neural tube closes and divides into three distinct pouches. The hindbrain controls the most basic survival functions: breathing, heart rate, blood pressure, and sleep. This bottom-up building sequence, where the brain’s most primitive structures come online before its more complex ones, continues all the way through early adulthood.
How the Brain Starts as a Tube
The entire brain and spinal cord originate from a flat strip of cells called the neural plate, which rolls into a hollow tube during the third week of pregnancy. By about day 24, the top end of this tube closes. The bottom end seals around day 26, and by week 4 the neural tube is fully closed.
Before that closure is even complete, the top of the tube starts to balloon outward into three pouches called primary brain vesicles. The rearmost pouch, the rhombencephalon, is the embryonic precursor of the hindbrain. The middle pouch, the mesencephalon, becomes the midbrain. The front pouch, the prosencephalon, eventually becomes the forebrain, which includes the cerebral cortex and all the higher-order thinking structures that define human cognition.
By week 5, these three pouches subdivide further into five secondary vesicles. The hindbrain splits into the structures that will become the cerebellum (which coordinates movement) and the medulla oblongata (which manages breathing, swallowing, and heart rate). Also at week 5, the forebrain begins producing early forms of the hippocampus, amygdala, and cerebral cortex, though these structures won’t be functional for months.
Why the Hindbrain Develops First
The hindbrain takes priority because it handles the functions a fetus needs to survive. Dedicated clusters of neurons within the hindbrain regulate respiration, blood circulation, motor coordination, and sleep. These are non-negotiable biological processes. Without a functioning brainstem, no other brain region matters.
During early development, the hindbrain organizes itself into repeating segments called rhombomeres, a highly conserved pattern seen across virtually all vertebrates. Genes that set up these segments activate earlier than nearly any other brain-patterning genes. In embryos, the first group of patterning genes switches on in the presumptive hindbrain region at the gastrula stage, before segmentation has even begun. This early genetic activation is part of why the hindbrain is structurally ahead of other brain regions from the very start.
The brainstem’s autonomic regulation doesn’t become fully active immediately, though. Functional milestones unfold gradually. The parasympathetic nervous system, which slows heart rate and supports rest, shows its first real maturation surge at the end of the second trimester, around weeks 26 to 28. Sympathetic activation, which handles the “fight or flight” response, ramps up during the transition from the late second into the early third trimester. By near-term, fetal breathing efforts are robust enough to produce detectable fluctuations in heart rate.
The Middle and Upper Brain Follow
After the hindbrain establishes its basic architecture, the midbrain and forebrain structures build outward in sequence. The midbrain, sitting between the brainstem and forebrain, processes sensory information and helps coordinate eye movement and auditory reflexes. It forms its primary vesicle at week 4 alongside the other two regions but remains relatively small compared to the forebrain, which undergoes enormous expansion over the following months.
The forebrain is where things get complex. By week 5, early precursors of the hippocampus (critical for memory) and the amygdala (involved in emotional processing) begin to appear. But “appear” is generous. The hippocampus doesn’t start taking its recognizable folded shape until weeks 13 to 14, and its internal structures continue infolding through weeks 15 and 16. Neuron production in one part of the hippocampus peaks around week 9, while another part peaks at week 14, and new neurons continue to be generated there through at least week 32.
The cerebral cortex, the wrinkled outer layer responsible for language, reasoning, and conscious thought, follows an even longer timeline. Cortical folding and volumetric growth follow a strict spatiotemporal schedule that begins in the second trimester. A 2023 study published in Nature, analyzing over 1,400 fetal brain volumes, found that detectable brain asymmetries, including regions associated with language, emerge as early as 14 weeks, with peak asymmetries appearing between 20 and 26 weeks.
The Prefrontal Cortex Finishes Last
If the hindbrain is the first chapter, the prefrontal cortex is the last. Located just behind the forehead, this region handles impulse control, long-term planning, social judgment, and decision-making. It is one of the last brain regions to reach full maturity, completing its development around age 25.
During adolescence and early adulthood, the prefrontal cortex undergoes continuous reconstruction, consolidation, and rewiring. This process begins at puberty and extends for over a decade. It’s the reason teenagers can be intellectually brilliant but still make impulsive choices: the hardware for reasoning is mostly built, but the wiring that connects it to emotional regulation and long-term consequences is still being refined. The full span of brain development, from the neural tube closing at week 4 of pregnancy to the prefrontal cortex maturing in the mid-20s, covers roughly 25 years.
Why Folate Matters in the Earliest Days
Because the neural tube forms and closes so early, often before many people even know they’re pregnant, the nutritional environment during weeks 3 and 4 is critical. Folic acid plays a direct role in this process. The rapidly dividing cells of the developing neural tube need to produce enormous quantities of DNA building blocks called nucleotides. Without enough folate, cell division slows and the neural folds may fail to close properly, leading to neural tube defects like spina bifida or anencephaly.
Folic acid supplementation works by increasing the availability of folate to these neuroepithelial cells, essentially ensuring they have enough raw material to keep up with the pace of growth. This is why health guidelines recommend taking folic acid before conception and through the first trimester, not just after a positive pregnancy test. By the time most people confirm a pregnancy at 5 or 6 weeks, the neural tube has already closed or failed to.