Germ layers and neural crest
Bilaminar and trilaminar disc, germ layer derivatives and neural crest
Weeks 2 and 3 of development for FCPS Part 1: bilaminar disc, gastrulation, what each germ layer forms, and neural crest derivatives and diseases. Know the odd ones out (iris muscles, adrenal medulla, microglia) and the recall questions follow.
Week 2: the week of twos
- The embryoblast forms a bilaminar disc: epiblast (dorsal, columnar) and hypoblast (ventral, cuboidal).
- Two cavities: the amniotic cavity above the epiblast and the yolk sac below the hypoblast.
- Two trophoblast layers: cytotrophoblast and syncytiotrophoblast.
- Extraembryonic mesoderm (derived from yolk sac cells in the classic account) fills the space between trophoblast and the embryo, then splits around a new cavity, the extraembryonic coelom (chorionic cavity), into somatic and splanchnic layers. The embryo hangs in it by the connecting stalk, the future umbilical cord.
- The prechordal plate, a thickening of hypoblast at the head end, marks the future mouth.
Week 3: gastrulation
- The primitive streak appears on the epiblast at the start of week 3 (about day 15) and defines the cranial–caudal axis and left and right sides.
- Epiblast cells move through the streak to form endoderm (replacing the hypoblast) and mesoderm; the epiblast left behind becomes ectoderm. So all three germ layers come from the epiblast.
- At two places ectoderm and endoderm stay stuck together with no mesoderm between them: the oropharyngeal (buccopharyngeal) membrane at the head end and the cloacal membrane at the tail end. Both later break down to open the mouth and the anal and urogenital outlets.
- The notochord grows from the primitive node, induces the overlying ectoderm to form the neural plate, and organises the vertebral bodies. Its only adult remnant is the nucleus pulposus; leftover cells can form a chordoma (clivus or sacrum).
- The streak normally regresses. Persisting remnants form a sacrococcygeal teratoma, the commonest tumour of the newborn, containing tissues of all three layers.
- Caudal dysgenesis (caudal regression): too little mesoderm forms at the tail end, giving absent sacrum, small fused legs, renal anomalies and a neurogenic bladder. It is most strongly linked with poorly controlled maternal diabetes; HbA1c before conception best predicts the risk.
Mesoderm subdivisions
| Mesoderm | Forms |
|---|---|
| Paraxial | Somites: sclerotome (vertebrae, ribs), myotome (skeletal muscle), dermatome (dermis of the back). Somites appear from day 20 at about three pairs a day: about 34–35 pairs at day 30, 42–44 in all; they are used to date the embryo |
| Intermediate | Kidneys, ureters, gonads, genital ducts |
| Lateral plate | Somatic layer: body wall, limb bones and connective tissue, parietal serosa. Splanchnic layer: gut wall muscle and connective tissue, visceral serosa, heart |
Teratogens act most powerfully during weeks 3–8, the period of organogenesis.
Germ layer derivatives
| Layer | Main derivatives |
|---|---|
| Surface ectoderm | Epidermis, hair, nails, lens, cornea epithelium, enamel, anterior pituitary (Rathke pouch), parotid gland, mammary and sweat glands, inner ear membranous labyrinth including the organ of Corti (otic placode), anal canal below the pectinate line |
| Neuroectoderm (neural tube) | Brain and spinal cord, retina (both layers) and optic nerve, posterior pituitary, pineal, astrocytes, oligodendrocytes, ependyma, sphincter and dilator pupillae |
| Neural crest | See next section |
| Mesoderm | Muscle (except iris), bone and cartilage of the trunk and limbs, dermis, heart, vessels, blood cells, spleen, kidneys and gonads, adrenal cortex, serous membranes, microglia (via monocytes), Kupffer cells |
| Endoderm | Epithelium of the gut, hepatocytes and bile ducts, pancreas, thyroid follicular cells, parathyroids, thymus epithelium, respiratory epithelium, bladder and urethra epithelium, middle ear and auditory tube, tonsil crypts |
- The posterior pituitary is a downgrowth (infundibulum) of the diencephalon, so it is neuroectoderm; damage to the stalk causes diabetes insipidus while the anterior lobe (surface ectoderm of Rathke pouch) keeps working.
- Dermoid cysts form where surface ectoderm is trapped along a line of fusion. The classic site is the outer end of the eyebrow (external angular dermoid at the frontozygomatic suture), present from birth and containing keratin and hair. Excise intact; rupture causes inflammation and recurrence.
- A teratoma contains tissues of all three germ layers; a dermoid cyst of the ovary is a mature cystic teratoma.
Neural crest
Neural crest cells separate from the edges of the neural folds as they close, and migrate widely. They are sometimes called the fourth germ layer.
- Peripheral nervous system: dorsal root ganglia, sensory ganglia of cranial nerves, sympathetic and parasympathetic ganglia, enteric neurones, Schwann cells.
- Melanocytes: neural crest cells reach the epidermis in the third month and make melanin.
- Adrenal medulla (chromaffin cells) and parafollicular C cells of the thyroid (calcitonin).
- Pia and arachnoid (dura is mostly mesoderm).
- Head and neck mesenchyme: facial bones and skull vault, pharyngeal arch cartilages, odontoblasts (dentine), dermis and smooth muscle of the face, ciliary muscle and corneal stroma.
- Heart: the aorticopulmonary (conotruncal) septum.
| Neurocristopathy | Crest defect |
|---|---|
| Hirschsprung disease | Enteric ganglion cells fail to reach the distal colon |
| DiGeorge syndrome | Crest contribution to 3rd and 4th pouches and conotruncus |
| Neuroblastoma, phaeochromocytoma | Tumours of adrenal medulla and sympathetic tissue |
| Melanoma | Malignant melanocytes |
| Neurofibromatosis, Waardenburg syndrome | Schwann cell and melanocyte disorders |
Body folding (week 4)
Head-to-tail and lateral folding turn the flat disc into a cylinder, bring the heart and septum transversum into the chest, and pinch the gut off from the yolk sac, leaving the vitelline duct.
Remember All three germ layers come from the epiblast; the notochord leaves only the nucleus pulposus.
Exam trap The adrenal medulla is neural crest but the adrenal cortex is mesoderm; thyroid follicular cells are endoderm but C cells are neural crest.
Exam trap The iris muscles are neuroectoderm, an exception to "all muscle is mesoderm".
How FCPS asks about this
- Where ectoderm meets endoderm with no mesoderm: oropharyngeal and cloacal membranes.
- Origin of all three germ layers: epiblast through the primitive streak (week 3); streak remnant gives sacrococcygeal teratoma.
- Neural crest cells in the epidermis in month 3: melanocytes making melanin.
- Origin of primordial germ cells: wall of the yolk sac.
- Lobe causing diabetes insipidus after stalk injury: posterior pituitary, from diencephalic neuroectoderm.
- Lump at the outer eyebrow since birth containing hair: dermoid cyst from ectoderm trapped at a fusion line.
- Absent sacrum and neurogenic bladder in a newborn: caudal regression, linked to maternal diabetes.
Test yourself on this topic
5 of the 54 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
In week 3 the bilaminar disc becomes trilaminar. Which cells give rise to all three germ layers of the embryo?
Answer: Epiblast, via the primitive streak
Gastrulation begins with the primitive streak on the epiblast surface. Epiblast cells move to the streak and invaginate: the first displace the hypoblast to form definitive endoderm, and later ones spread between the layers as intraembryonic mesoderm. The epiblast cells that remain on the surface form the ectoderm. Thus all three germ layers come from the epiblast, and the hypoblast contributes only to extraembryonic tissue.
Gastrulation
- Primitive streak on epiblast
- First cells: endoderm
- Next cells: mesoderm
- Remaining epiblast: ectoderm
Remember Epiblast makes the embryo; hypoblast makes membranes.
Exam trap Endoderm is not from hypoblast; epiblast cells replace the hypoblast.
Why the other options are wrong
- Hypoblast cells replacing the epiblast Hypoblast is displaced by epiblast-derived endoderm.
- Cytotrophoblast cells of the chorion Trophoblast forms the placenta, not the embryo.
- Notochordal cells spreading laterally The notochord is itself formed from epiblast cells at the node.
- Extraembryonic mesoderm cells of the stalk Extraembryonic mesoderm forms membranes and the cord, not the embryo.
A newborn has bilateral congenital cataracts. From which embryonic tissue does the affected structure develop?
Answer: Surface ectoderm
A cataract is an opacity of the lens. The lens develops from the lens placode, a thickening of surface ectoderm induced by the underlying optic vesicle in week 4. The placode invaginates to form the lens vesicle, whose posterior cells elongate into the primary lens fibres. The retina and pupil muscles come from neuroectoderm, while the corneal stroma and sclera come largely from neural crest mesenchyme.
Lens origin
- Optic vesicle induces surface ectoderm
- Lens placode then lens vesicle
- Cataract = opacity of this ectodermal lens
- Retina is neuroectoderm
Remember Lens and corneal epithelium: surface ectoderm.
Exam trap The lens sits inside the eye but does not come from the optic cup.
Why the other options are wrong
- Neuroectoderm of the optic cup Forms the retina and iris epithelium, not the lens.
- Neural crest mesenchyme Forms corneal stroma, sclera and much of the uvea.
- Paraxial mesoderm Forms the extraocular muscles.
- Pharyngeal endoderm Forms the lining of the pharynx and its pouches.
A 62-year-old man has sacral pain and constipation. MRI shows a destructive midline sacral mass. Biopsy shows lobules of large cells with bubbly, vacuolated cytoplasm in a mucoid matrix, positive for brachyury. What is the origin of this tumour?
Answer: Notochord remnants
The notochord induces the neural plate and the vertebral column, and then largely disappears except as the nucleus pulposus. Small remnants can persist along the axis, especially at the clivus and sacrum, and give rise to chordomas. These slow-growing, locally destructive tumours contain physaliphorous (bubble-bearing) cells and express brachyury, a notochordal transcription factor. Wide surgical excision is the main treatment because they recur locally.
Chordoma
- From notochord remnants
- Sites: sacrum, clivus
- Physaliphorous cells
- Brachyury positive
Remember Bubbly cells in a midline sacral mass: chordoma.
Exam trap The nucleus pulposus is the only normal adult notochord derivative.
Why the other options are wrong
- Primitive streak remnants Give sacrococcygeal teratomas, mostly in infants.
- Neural crest cells Give tumours such as neuroblastoma and schwannoma.
- Sclerotome cartilage Gives chondrosarcoma, which lacks brachyury.
- Ependymal cells of the filum Gives myxopapillary ependymoma, not this histology.
A firm lump at the outer end of a child's eyebrow since birth contains keratin and hair. How did it form?
Answer: Ectoderm trapped at a line of fusion
An external angular dermoid lies at the frontozygomatic suture, where facial processes meet during development. Surface ectoderm becomes trapped beneath the skin along this line of fusion and forms a cyst lined by skin with hair follicles and sebaceous glands, filled with keratin. It is present from birth and may scallop the underlying bone. Midline dermoids, especially at the nose, need imaging before excision because they can extend intracranially.
External angular dermoid
- At frontozygomatic suture
- Trapped surface ectoderm
- Contains keratin and hair
- Midline nasal dermoid: image first
Remember Lump at the outer eyebrow since birth: angular dermoid.
Exam trap Rupture during removal causes inflammation and recurrence, so excise intact.
Why the other options are wrong
- Endoderm remnant of a pharyngeal pouch Pouch remnants form branchial cysts in the neck.
- Neural tissue herniating through bone This is an encephalocele, which is soft and may pulsate.
- Lymphatic sac failing to join veins This gives a cystic hygroma.
- Mesoderm forming a vascular tumour This gives a haemangioma, which is soft and red or blue.
After transsphenoidal surgery that damaged the pituitary stalk, a man passes 8 litres of dilute urine a day, while his anterior pituitary hormones remain normal. The damaged lobe developed from which of the following?
Answer: Neuroectoderm of the diencephalon
The pituitary has a dual origin. The posterior lobe (neurohypophysis) and stalk grow down from the floor of the diencephalon as the infundibulum, so they are neuroectoderm. They store and release ADH and oxytocin made by hypothalamic neurons. The anterior lobe comes from Rathke pouch, an upgrowth of oral ectoderm from the roof of the stomodeum. Stalk damage interrupts ADH delivery and causes cranial diabetes insipidus, while anterior lobe function may be preserved.
Pituitary origins
- Posterior: neuroectoderm (infundibulum)
- Anterior: oral ectoderm (Rathke pouch)
- Stalk damage: diabetes insipidus
- Craniopharyngioma from Rathke remnant
Remember Posterior pituitary is brain; anterior is mouth.
Exam trap Diabetes insipidus after pituitary surgery can follow a triphasic pattern with a phase of SIADH.
Why the other options are wrong
- Oral ectoderm of Rathke pouch Forms the anterior lobe, which is working.
- Endoderm of the pharyngeal roof The pharyngeal roof does not form the pituitary.
- Neural crest of the first arch Not a pituitary source.
- Mesoderm around the notochord Forms the sphenoid bone around it, not the gland.
Where this sits in the CPSP syllabus
- Paper 1: General and systemic embryology, Bilaminar and trilaminar disc; germ layer derivatives; neural crest
- Surgery & Allied, Paper 2: Embryology for surgery, Bilaminar and trilaminar disc; germ layer derivatives; neural crest
- Diagnostic Radiology, Paper 2: Embryology, Germ layers, neural crest and neural tube; development of the brain and spine