Basic Neurosciences · Paper A
Neurulation: neural plate to neural tube closure
Your entire brain and spinal cord begins as a flat sheet on the embryo's back that rolls up and zips shut — and the zip has to finish inside the first four weeks after fertilisation. Neurulation is that rolling-up: the neural plate becomes the neural tube, sealing from the middle outwards so that the head end and the tail end are the last two places to close. Everything examinable here hangs off that geometry. The head end (the anterior neuropore) closes around day 25 and the tail end (the posterior neuropore) around day 28, so a failure at the head end gives anencephaly and a failure at the tail end gives spina bifida. For a psychiatrist the point is not the embryology for its own sake: it is that the drugs you prescribe to women of childbearing age, sodium valproate above all, act on a window that has already shut by about six weeks of pregnancy.
The process starts with a signal, not with the nervous system. A rod of midline tissue called the notochord induces the ectoderm lying directly above it to thicken, and that thickened strip is the neural plate — so the first nervous tissue exists only because a neighbouring structure told it to. Around day 20 the long edges of the plate rise into neural folds with a neural groove running between them, and the folds lean towards each other over the groove. Around day 22 the folds touch and fuse at roughly the level of the future neck, and that first point of fusion then extends in both directions along the embryo, converting the open groove into a closed tube behind it as it travels. Because fusion is spreading outwards from a mid-point, two openings persist at either end while the middle is already sealed: the anterior neuropore towards the head and the posterior neuropore towards the tail. The anterior neuropore closes around day 25 and the posterior around day 28, at which point the central nervous system is a continuous sealed tube whose fluid-filled lumen goes on to become the ventricles of the brain and the central canal of the spinal cord. One population of cells does not stay for any of this: cells at the crests of the folds detach as the folds fuse and migrate away as neural crest, going on to form the sensory and autonomic ganglia, Schwann cells, the adrenal medulla, melanocytes and much of the facial skeleton — which is why a question about the peripheral nervous system's origin is answered by the crest and never by the tube.
A woman with bipolar disorder, well for years on sodium valproate, tells you at her review that she is six weeks pregnant. You want to know what you can still change. The honest answer is that the part of her baby's development this drug most threatens has just closed. Her baby's brain and spinal cord started life as a flat sheet of cells on the embryo's back, and that sheet rolls into a tube and seals shut inside the first month. Everything psychiatry needs from embryology sits in that one narrow window, so this page walks through it day by day.
Neurulation turns a flat plate of cells into the hollow tube your entire central nervous system (the brain and spinal cord together) grows out of. The raw material is ectoderm (the outermost of the three cell layers an early embryo builds itself from). A rod of tissue running down the embryo's midline, the notochord, signals to the ectoderm lying directly over it, and those cells thicken into the neural plate. The plate then curls along its length, its two long edges rise and meet in the midline, and they fuse into a closed, fluid-filled tube. That tube becomes the whole of the future brain and spinal cord.
Picture the tube sealing from the head downwards and you will get most of this topic wrong. Fusion starts in the middle, at about the level of the future neck, and then travels in BOTH directions at once — one run towards the head, one towards the tail. Because it travels outwards from the middle, the two ENDS of the tube are the last parts to seal, and each end can fail on its own.
That single fact explains why one embryo finishes with a defect at the head end and a perfectly normal spine, and another finishes with the reverse. One caveat on the caveat: exams teach a single starting point running both ways, while research has proposed several separate starting points in humans. Learn the one-zip picture, and know that it is a teaching simplification rather than settled anatomy.
Work out what a closing zip actually has to do. It has to bring two moving edges into contact, hold them together, and fuse them, all while the embryo is still growing underneath. Anywhere the zip has already passed, the tube is sealed and safe. The only vulnerable places are wherever the zip has not yet reached — which, because it started in the middle, means the two open ends.
Those two openings have names. The one at the head end is the anterior (rostral) neuropore; the one at the tail end is the posterior (caudal) neuropore. Around day 25 after fertilisation the anterior neuropore closes, and around day 28 the posterior neuropore closes. Miss either deadline and the nervous system stays open to the outside at that end for the rest of development.
That gives you the two classic outcomes without memorising a list. An anterior neuropore that never closes leaves the forebrain exposed and destroyed: anencephaly, which is not survivable. A posterior neuropore that never closes leaves the lower cord and its coverings exposed: spina bifida, at its most severe a myelomeningocele, where cord and meninges (the membranes wrapping the cord) protrude through the gap in the back.
The dating is where candidates come unstuck, because embryologists count from fertilisation and obstetricians count from the last menstrual period, and the two differ by about two weeks.
For example, take a woman with a regular 28-day cycle who conceives on day 14. Her neural tube completes closure 28 days after that, on day 42 of her cycle. Counted the obstetric way, day 42 is six weeks of gestation. Her period was due at four weeks, so the tube finished closing roughly two weeks AFTER the missed period — often before a first midwife appointment, but not, as the folklore has it, before she could possibly have known.
Now put a number on the risk. A neural tube defect occurs in roughly 1 in 1,000 pregnancies in the UK. Exposure to sodium valproate raises that to somewhere around 1 to 2 in 100 — roughly ten to twenty times the background rate, and that is on top of valproate's separate effects on later cognitive development.
Every wrong answer on this topic is a real developmental event sitting next to neurulation in time or in space. Check your own instinct against this table before you commit.
| Confused with neurulation | The one feature that separates it |
|---|---|
| Gastrulation | Happens just before, and makes the three germ layers; neurulation then acts on only one of them |
| Neural crest migration | Cells that break away from the tops of the folds and leave; they become peripheral nerves and ganglia, not the tube |
| Somitogenesis | Blocks of tissue forming beside the tube; they become vertebrae and muscle, with no nervous tissue in them |
| Organogenesis | The umbrella term for weeks three to eight as a whole; neurulation is one named event inside it |
Nobody diagnoses neurulation itself; what gets diagnosed is its failure, and antenatal screening does the work. The routine 18-to-20-week anomaly ultrasound scan is the main investigation, and it detects the great majority of open defects: anencephaly is usually visible earlier still, at the 11-to-14-week dating scan, because the skull vault simply is not there. Raised alpha-fetoprotein in maternal blood is the older marker for an open defect and is largely historical in UK practice now that scanning does the job. Spina bifida occulta is different again: no open defect, often nothing to see on any scan, and frequently found by accident on a spine x-ray taken for something else.
You cannot treat a neural tube after day 28, so management means getting folic acid in beforehand. UK practice, set out in the BNF, is 400 micrograms of folic acid daily from before conception until the twelfth week of pregnancy, raised to 5 milligrams daily for women at higher risk — a previous affected pregnancy, diabetes, a body mass index over 30, sickle cell disease, or treatment with an antiepileptic medicine. Notice the second and last of those: they are your patients.
For anyone prescribing valproate, the MHRA Valproate Pregnancy Prevention Programme is the binding UK framework — valproate must not be used in a woman able to become pregnant unless the conditions of that programme are met, which include highly effective contraception and an annual specialist review. NICE NG97 governs dementia rather than this, so do not reach for it here; the guidance you need is the MHRA programme and the BNF's folic acid entry, and you should be able to name both.
The high-yield move is to read the defect backwards to the deadline. A picture or a description of a missing skull vault and destroyed forebrain means the anterior neuropore missed day 25; a lesion over the lower back means the posterior neuropore missed day 28. Test yourself before moving on: if the zip runs outwards from the middle in both directions, can you explain why a single embryo almost never has a defect in the middle of its spine?
Remember it this way: the neural plate rolls into a tube that zips shut from the middle outwards, the head end sealing around day 25 and the tail end around day 28, so an unclosed anterior neuropore gives anencephaly, an unclosed posterior neuropore gives spina bifida, and folic acid started before conception is the only thing that moves the odds.