Neural System Development

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Stage10 sem6.jpg


Neural groove closing to neural tube, early week 4
(Stage 10)
Brain size embryonic (week 4, 5, 6, and 8) and late fetal (third trimester)
Relative brain size embryonic (week 4, 5, 6, and 8) and late fetal (third trimester)

Neural development is one of the earliest systems to begin and the last to be completed after birth. This development generates the most complex structure within the embryo and the long time period of development means in utero insult during pregnancy may have consequences to development of the nervous system.

The early central nervous system begins as a simple neural plate that folds to form a groove then tube, open initially at each end. Failure of these opening to close contributes a major class of neural abnormalities (neural tube defects).

Within the neural tube stem cells generate the 2 major classes of cells that make the majority of the nervous system : neurons and glia. Both these classes of cells differentiate into many different types generated with highly specialized functions and shapes. This section covers the establishment of neural populations, the inductive influences of surrounding tissues and the sequential generation of neurons establishing the layered structure seen in the brain and spinal cord.

  • Neural development beginnings quite early, therefore also look at notes covering Week 3 - neural tube and Week 4 - early nervous system.
  • Development of the neural crest and sensory systems (hearing/vision/smell) are only introduced in these notes and are covered in detail in other notes sections.

Neural Links: Introduction | Ventricular System | Stage 22 | Gliogenesis | Fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | Neural Crest | Sensory | Abnormalities | Folic Acid | Iodine Deficiency | Fetal Alcohol Syndrome | Postnatal | Postnatal - Neural Examination | Histology | Historic Neural | Category:Neural
Neural Parts: Introduction | Prosencephalon | Telencephalon | Amygdala | Hippocampus | Basal Ganglia | lateral ventricles | Diencephalon | Epithalamus | Thalamus | Hypothalamus | Pituitary | Pineal | third ventricle | Mesencephalon | Mesencephalon | Tectum | cerebral aqueduct | Rhombencephalon | Metencephalon | Pons | Cerebellum | Myelencephalon | Medulla Oblongata | Spinal Cord | Vascular | Meninges | Category:Neural
Historic Neural Embryology  
1883 Nervous System | 1892 Nervous System Development | 1900 fourth ventricle | 1905 Brain Blood-Vessels | 1909 corpus ponto-bulbare | 1912 nuclei pontis - nucleus arcuatus | 1921 Neural Development | 1921 Anencephaly | 1921 Brain Weight | 1921 Brain Vascular System | 1921 Cerebellum | 1922 Brain Plan | 1923 Neural Folds | 1904 Brain and Mind | 1904 Brain Structure | 1909 Forebrain Vesicle | 1922 Hippocampal Fissure | 1923 Forebrain | 1927 Anencephaly | 1937 Anencephaly | 1945 Spinal Cord | Santiago Ramón y Cajal | Ziegler Neural Models | Historic Embryology Papers | Historic Disclaimer

Some Recent Findings

  • Secondary neurulation of human embryos: morphological changes and the expression of neuronal antigens[1] "The morphological changes and expression patterns of neuronal antigens of human embryos, obtained from the therapeutic termination of pregnancy or from surgical procedures, were analyzed in order to characterize the secondary neurulation. ...The formation of the caudal neural tube to the tip of the caudal portion of the embryo was finished at stage 17. The postcloacal gut had completely disappeared at stage 18, and multiple cavities of the caudal neural tube were clearly visible. The caudal portion of the neural tube showed findings suggestive of involution at stage 19. The expression patterns of neuronal antigens were as follows: N-CAM and NeuN showed immunoreactivity at the germinal layer of the spinal cord at stages 17 and 18. Neurofilament-associated protein (3A10) showed persistent immunoreactivity at the caudal cell mass and notochord during the observation period, along with the spinal cord, and the positive reactions were mainly located at the dorsal white matter at stage 17. Synaptophysin showed a weak positive reaction at the caudal cell mass and notochord at stages 13 and 14, evident by staining observed at the spinal cord at stages 15 and 16. There was no definite positive reaction for GFAP."
  • Neural induction and early patterning in vertebrates[2] "Work on the molecular circuitry underlying neural induction, also in the same model system, demonstrated that elimination of ongoing transforming growth factor-β (TGFβ) signaling in the ectoderm is the hallmark of anterior neural-fate acquisition. This observation is the basis of the 'default' model of neural induction. Endogenous neural inducers are secreted proteins that act to inhibit TGFβ ligands in the dorsal ectoderm. In the ventral ectoderm, where the signaling ligands escape the inhibitors, a non-neural fate is induced. Inhibition of the TGFβ pathway has now been demonstrated to be sufficient to directly induce neural fate in mammalian embryos as well as pluripotent mouse and human embryonic stem cells."
More recent papers  
Mark Hill.jpg
PubMed logo.gif

This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Neural System Embryology

Joel C Glover, Karen L Elliott, Albert Erives, Victor V Chizhikov, Bernd Fritzsch Wilhelm His' lasting insights into hindbrain and cranial ganglia development and evolution. Dev. Biol.: 2018; PubMed 29447907

Enrique J Cobos, Chelsea A Nickerson, Fuying Gao, Vijayendran Chandran, Inmaculada Bravo-Caparrós, Rafael González-Cano, Priscilla Riva, Nick A Andrews, Alban Latremoliere, Corey R Seehus, Gloria Perazzoli, Francisco R Nieto, Nicole Joller, Michio W Painter, Chi Him Eddie Ma, Takao Omura, Elissa J Chesler, Daniel H Geschwind, Giovanni Coppola, Manu Rangachari, Clifford J Woolf, Michael Costigan Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling. Cell Rep: 2018, 22(5);1301-1312 PubMed 29386116

Agnieszka Oponowicz, Anna Kozłowska, Sławomir Gonkowski, Janusz Godlewski, Mariusz Majewski Changes in the Distribution of Cocaine- and Amphetamine-Regulated Transcript-Containing Neural Structures in the Human Colon Affected by the Neoplastic Process. Int J Mol Sci: 2018, 19(2); PubMed 29385033

Hana Hříbková, Marta Grabiec, Dobromila Klemová, Iva Slaninová, Yuh-Man Sun Five steps to form neural rosettes: structure and function. J. Cell. Sci.: 2018; PubMed 29361526

Ping Li, Heng-Xi Li, Hong-Yan Jiang, Lie Zhu, Hai-Ying Wu, Jin-Tao Li, Jiang-Hua Lai Expression of NG2 and platelet-derived growth factor receptor alpha in the developing neonatal rat brain. Neural Regen Res: 2017, 12(11);1843-1852 PubMed 29239330

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice[3] "Proliferating neural stem cells and intermediate progenitors persist in the ventricular-subventricular zone (V-SVZ) of the adult mammalian brain. This extensive germinal layer in the walls of the lateral ventricles is the site of birth of different types of interneurons destined for the olfactory bulb. The cell cycle dynamics of stem cells (B1 cells), intermediate progenitors (C cells), and neuroblasts (A cells) in the V-SVZ and the number of times these cells divide remain unknown. Using whole mounts of the walls of the lateral ventricles of adult mice and three cell cycle analysis methods using thymidine analogs, we determined the proliferation dynamics of B1, C, and A cells in vivo."
  • Dynamic imaging of mammalian neural tube closure[4] "Here we use laser point scanning confocal microscopy of a membrane expressed fluorescent protein to visualize the dynamic cell behaviors comprising neural tube closure in the cultured mouse embryo. In particular, we have focused on the final step wherein the neural folds approach one another and seal to form the closed neural tube. Our unexpected findings reveal a mechanism of closure in the midbrain different from the zipper-like process thought to occur more generally. Individual non-neural ectoderm cells on opposing sides of the neural folds undergo a dramatic change in shape to protrude from the epithelial layer and then form intermediate closure points to "button-up" the folds. Cells from the juxtaposed neural folds extend long and short flexible extensions and form bridges across the physical gap of the closing folds."
  • Apoptosis is not required for mammalian neural tube closure[5] "Apoptotic cell death occurs in many tissues during embryonic development and appears to be essential for processes including digit formation and cardiac outflow tract remodeling. Studies in the chick suggest a requirement for apoptosis during neurulation, because inhibition of caspase activity was found to prevent neural tube closure. In mice, excessive apoptosis occurs in association with failure of neural tube closure in several genetic mutants, but whether regulated apoptosis is also necessary for neural tube closure in mammals is unknown. Here we investigate the possible role of apoptotic cell death during mouse neural tube closure. We confirm the presence of apoptosis in the neural tube before and during closure, and identify a correlation with 3 main events: bending and fusion of the neural folds, postfusion remodeling of the dorsal neural tube and surface ectoderm, and emigration of neural crest cells."


Human embryo cortex (Week 8, Carnegie stage 22)
  1. Understand early neural development.
  2. Understand the formation of spinal cord.
  3. Understand the formation of the brain; grey and white matter from the neural tube.
  4. Understand the role of migration of neurons during neural development.
  5. To know the main derivatives of the brain vesicles and their walls.
  6. To know how the nervous system is modelled, cell death etc.
  7. To understand the contribution of the neural crest.
  8. Understand the developmental basis of certain congenital anomalies of the nervous system, including hydrocephalus, spina bifida, anencephaly and encephalocele.


UNSW Embryology

Logo.png Citation: Hill, M.A. (2018). UNSW Embryology (18th ed.) Retrieved February 22, 2018, from
Neural Links: Introduction | Ventricular System | Stage 22 | Gliogenesis | Fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | Neural Crest | Sensory | Abnormalities | Folic Acid | Iodine Deficiency | Fetal Alcohol Syndrome | Postnatal | Postnatal - Neural Examination | Histology | Historic Neural | Category:Neural
Neural Parts: Introduction | Prosencephalon | Telencephalon | Amygdala | Hippocampus | Basal Ganglia | lateral ventricles | Diencephalon | Epithalamus | Thalamus | Hypothalamus | Pituitary | Pineal | third ventricle | Mesencephalon | Mesencephalon | Tectum | cerebral aqueduct | Rhombencephalon | Metencephalon | Pons | Cerebellum | Myelencephalon | Medulla Oblongata | Spinal Cord | Vascular | Meninges | Category:Neural

The Developing Human: Clinically oriented embryology

Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders. (links only function with UNSW connection)

The Developing Human, 10th edn.jpg
The Developing Human: Clinically Oriented Embryology (10th edn) 
The Developing Human, 10th edn.jpg

UNSW Students have online access to the current 10th edn. through the UNSW Library subscription (with student Zpass log-in).

APA Citation: Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders.

Links: UNSW Embryology Textbooks | Embryology Textbooks | UNSW Library
  1. Introduction to the Developing Human
  2. First Week of Human Development
  3. Second Week of Human Development
  4. Third Week of Human Development
  5. Fourth to Eighth Weeks of Human Development
  6. Fetal Period
  7. Placenta and Fetal Membranes
  8. Body Cavities and Diaphragm
  9. Pharyngeal Apparatus, Face, and Neck
  10. Respiratory System
  11. Alimentary System
  12. Urogenital System
  13. Cardiovascular System
  14. Skeletal System
  15. Muscular System
  16. Development of Limbs
  17. Nervous System
  18. Development of Eyes and Ears
  19. Integumentary System
  20. Human Birth Defects
  21. Common Signaling Pathways Used During Development
  22. Appendix : Discussion of Clinically Oriented Problems

Larsen's human embryology

Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone. (links only function with UNSW connection)

Larsen's human embryology 5th ed.jpg
Larsen's Human Embryology (5th edn) 
Larsen's human embryology 5th ed.jpg
UNSW students have full access to this textbook edition through UNSW Library subscription (with student Zpass log-in).

APA Citation: Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.

Links: UNSW Embryology Textbooks | Embryology Textbooks | UNSW Library
  1. Gametogenesis, Fertilization, and First Week
  2. Second Week: Becoming Bilaminar and Fully Implanting
  3. Third Week: Becoming Trilaminar and Establishing Body Axes
  4. Fourth Week: Forming the Embryo
  5. Principles and Mechanisms of Morphogenesis and Dysmorphogenesis
  6. Fetal Development and the Fetus as Patient
  7. Development of the Skin and Its Derivatives
  8. Development of the Musculoskeletal System
  9. Development of the Central Nervous System
  10. Development of the Peripheral Nervous System
  11. Development of the Respiratory System and Body Cavities
  12. Development of the Heart
  13. Development of the Vasculature
  14. Development of the Gastrointestinal Tract
  15. Development of the Urinary System
  16. Development of the Reproductive System
  17. Development of the Pharyngeal Apparatus and Face
  18. Development of the Ears
  19. Development of the Eyes
  20. Development of the Limbs

Neural Movies

Neural Development
Neuralplate 001 icon.jpg
 ‎‎Neural Plate
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Neuraltube 001 icon.jpg
 ‎‎Neural Tube
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Secondary neurulation 01 icon.jpg
 ‎‎Secondary Neurulation
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 ‎‎Stage 13 Neural
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Stage13 MRI 3D02 icon.jpg
 ‎‎Embryo CNS
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Mouse neural tube 01 movie icon.jpg
 ‎‎Neural Tube Close
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Stage16 MRI 3D02 icon.jpg
 ‎‎Embryo CNS
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Stage16 MRI S01 icon.jpg
 ‎‎Embryo Stage 16
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Human embryo tomography Carnegie stage 17.jpg
 ‎‎Stage 17 Embryo
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 ‎‎Stage 22 Neural
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Stage23 MRI 3D02 icon.jpg
 ‎‎Embryo CNS
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Stage23 MRI S01 icon.jpg
 ‎‎Sagittal Head
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Abnormalities Ultrasound
Brain fissure development 03.jpg
 ‎‎Sylvian Fissure
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Adult human brain tomography.jpg
 ‎‎Adult Brain
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US Dandy-Walker 01.jpg
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US Spina bifida GA19week.jpg
 ‎‎Spina Bifida
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Links: Movies | Postnatal - Neural Examination Movies

Human Early Neural Development

Adult human brain

The stages below refer to specific Carneigie stages of development (modified from O'Rahilly and Müller 1994[6]).

  • Carnegie stage 8 - (about 18 postovulatory days) neural groove and folds are first seen
  • Carnegie stage 9 - the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open.
  • Carnegie stage 10 - (two days later) neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm
  • Carnegie stage 11 - (about 24 days) the rostral (or cephalic) neuropore closes within a few hours; closure is bidirectional, it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently.
  • Carnegie stage 12 - (about 26 days) The caudal neuropore takes a day to close.
    • the level of final closure is approximately at future somitic pair 31.
    • corresponds to the level of sacral vertebra 2.
  • Carnegie stage 13 - (4 weeks) the neural tube is normally completely closed.

Secondary neurulation begins at stage 12 - is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate.

Week 4 to Week 8

Embryonic Central Nervous System
Stage 13 Stage 14 Stage 16 Stage 21
Human Stage13 sagittal upper half01.jpg

scale bar = 1 mm

Human Stage14 neural01.jpg Human Stage16 neural03.jpg Human Stage21 neural01.jpg
Week 4 Week 5 Week 6 Week 8

Week 4 - Stage 13

Week 4 - Stage 16

Week 8 - Stage 23

The above MRI scan movie shows the structure of the central nervous system at the end of the embryonic period. Note the relative size and position of the CNS parts, the flexures, the size of the ventricular spaces and chord plexus within this space. There are additional Stage 23 movies available in the links below.

Stage 23 MRI Movies: Surface | Central Nervous System | CNS (labeled) | Sagittal | Sagittal (labeled) | Transverse | Transverse (labeled) | Coronal | Sagittal Head (labeled) | Sagittal GIT (labeled) | Carnegie stage 23

Week: 1 2 3 4 5 6 7 8
Carnegie stage: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Stage 23 Links: Week 8 | System Development | Lecture - Limb | Lecture - Head Development | Lecture - Sensory | Science Practical - Head | Science Practical - Sensory | Science Practical - Urogenital | Historic - Skull Development | Carnegie Embryos | Madrid Embryos | Category:Carnegie Stage 23 | Next Fetal Development
  Historic Papers: 1954 Stage 19-23

Carnegie Stages: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | About Stages | Timeline

Development Overview

Neuralation begins at the trilaminar embryo with formation of the notochord and somites, both of which underly the ectoderm and do not contribute to the nervous system, but are involved with patterning its initial formation. The central portion of the ectoderm then forms the neural plate that folds to form the neural tube, that will eventually form the entire central nervous system.

Early developmental sequence: Epiblast - Ectoderm - Neural Plate - Neural groove and Neural Crest - Neural Tube and Neural Crest

Neural Tube Primary Vesicles Secondary Vesicles Adult Structures
week 3 week 4 week 5 adult
neural plate
neural groove
neural tube

Prosencephalon Telencephalon Rhinencephalon, Amygdala, Hippocampus, Cerebrum (Cortex), Hypothalamus, Pituitary | Basal Ganglia, lateral ventricles
Diencephalon Epithalamus, Thalamus, Subthalamus, Pineal, third ventricle
Mesencephalon Mesencephalon Tectum, Cerebral peduncle, Pretectum, cerebral aqueduct
Rhombencephalon Metencephalon Pons, Cerebellum
Myelencephalon Medulla Oblongata
Spinal Cord


Does not contribute to the final nervous system, but is critical to patterning the development.

  • forms initially as the Axial Process, a hollow tube which extends from the primitive pit , cranially to the oral membrane
  • the axial process then allow transient communication between the amnion and the yolk sac through the neuroenteric canal.
  • the axial process then merges with the Endodermal layer to form the Notochordal Plate.
  • the notochordal plate then rises back into the Mesodermal layer as a solid column of cells which is the Notochord.

Links: Notochord


Two main parts with different morphology

  • columnar - midline neural plate forming neural tube and neural crest
  • cuboidal - lateral surface ectoderm forming epidermis and sensory placodes
    • epidermis of skin, hair, glands, anterior pituitary, teeth enamel
    • sensory placodes

Links: Ectoderm

Neural Plate

The neural plate forms above the notochord and paraxial mesoderm and extends from the buccopharyngeal membrane to primitive node. The cells are described as neuroectodermal and form initially two regions along the head to tail axis: a cranial broad plate region (brain plate) and caudally a narrower plate region (spinal cord).

Neural Determination

Neuronal populations are thought to be specified before the plate folds by signals from underlying notochord and mesoderm, as well as signals spread laterally through teh plate.

  • secrete noggin, chordin,follistatin
  • all factors bind BMP-4 an inhibitor of neuralation bone morphogenic protein acts through membrane receptor

Lateral Inhibition

  • generates at spinal cord level 3 strips of cells
  • expression of delta inhibits nearby cells, which express notch receptor, from becoming neurons
  • Delta-Notch- generates "neural strips"
Neuralplate 001 icon.jpg
 ‎‎Neural Plate
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Neural Bending

There are two bending processes occurring in the formation of the neural groove and neural tube.

  1. occuring in the midline due to cells in this region having a basal nuclear localisation. This initial bending leads to formation of the neural groove.
  2. occuring at the dorsolateral hinge points by different mechanism involving "buckling". This later bending leads to formation of the neural tube.

Mouse neural tube bending model.jpg

Mouse neural tube bending model (see review[7])

Neural Groove

  • forms in the midline of the neural plate (day 18-19)
  • either side of which are the neural folds
  • continues to deepen until about week 4
  • neural folds begins to fuse
  • at 4th somite level
Stage10 sem6.jpg

Carnegie stage 10 Week 4

Neural Tube

  • fusion of neural groove extends rostrally and caudally
  • begins at level of 4th somite, "zips up" neural groove
  • leaves 2 openings at either end- Neuropores
  • forms the brain and spinal cord
  • Secondary Neuralation - caudal end of neural tube formed by secondary neuralation, develops from primitive streak region, solid cord canalized by extension of neural canal. mesodermal caudal eminence


Cranial Neuropore Caudal Neuropore
Stage11 sem9.jpg Stage12 SEM3.jpg
(stage 11) (stage 12)
  • cranial (anterior) neuropore closes before caudal (posterior)
  • failure to close - Neural Tube Defects (NTD), severity dependent upon level, spina bifida anancephaly (More? [neuron2.htm Neural Abnormalities])
  • found that supplementation of maternal diet with folate reduces incidence of NTDs
    • A randomised controlled trial conducted by the Medical Research Council of the United Kingdom demonstrated a 72% reduction in risk of recurrence by periconceptional (ie before and after conception) folic acid supplementation (4mg daily).
    • Women who have one infant with a neural tube defect have a significantly increased risk of recurrence (40-50 per thousand compared with 2 per thousand for all births)

Neural Crest

  • a population of cells at the edge of the neural plate that lie dorsally when the neural tube fuses
  • dorsal to the neural tube, as a pair of streaks
  • cells migrate throughout the embryo
  • studied by quail-chick chimeras - transplanted quail cells have obvious nucleoli compared with chicken Neural Crest Derivitives
  • pluripotential, forms many different types of cells: dorsal root ganglia (neurons, sheath cells, glia), autonomic ganglia, adrenal medulla, pia-arachnoid sheath, skin melanocytes, connective tissue of cardiac outflow, thyroid parafollicular cells, craniofacial skeleton and teeth odontoblasts.
Links: Neural Crest Development

Early Brain Structure

Primary Vesicles

CNS primary vesicles.jpg

  • rostral neural tube forms 3 primary brain vesicles (week 4)
  • 3 primary vesicles: prosencephalon (forebrain), mesencephalon (midbrain), rhombencephalon (hindbrain)

See also the week 4 embryo movie.

Secondary Vesicles

CNS secondary vesicles.jpg

From the 3 primary vesicles developing to form 5 secondary vesicles (week 5)

  • prosencephalon- telencephalon (endbrain, forms cerebral hemispheres), diencephalon (betweenbrain, forms optic outgrowth)
  • mesencephalon
  • rhombencephalon- metencephalon (behindbrain), myelencephalon (medullabrain)

See also the week 6 embryo movie.

Carnegie Stage 14 Secondary Vesicles (Week 5)
Human Stage14 neural01.jpg Human Stage14 neural02.jpg
Cranial Nerves 
Nerve Number Name Type Origin Function
CN I Olfactory sensory telencephalon smell placode
CN II Optic sensory retinal ganglial cells vision
CN III Oculomotor motor anterior midbrain extraocular muscles eye movements and pupil dilation (motor)
CN IV Trochlear motor dorsal midbrain extraocular muscles (superior oblique muscle)
CN V Trigeminal motor/sensory pons proprioception, mastication
CN VI Abducent motor extraocular muscles control eye movements (lateral rectus muscle)
CN VII Facial motor/sensory pons facial expression, taste (tongue anterior and central regions) regulate salivary production.
CN VIII Acoustic sensory vestibular and cochlear nuclei hearing/balance placode
CN IX Glossopharyngeal motor/sensory medulla swallowing and speech, taste (tongue posterior region)
CN X Vagus motor/sensory medulla larynx and pharynx muscles (speech and swallowing), regulates heartbeat, sweating, and peristalsis
CN XI Accessory motor motor neurons sternocleidomastoid and trapezius muscles
CN XII Hypoglossal motor motor neurons tongue muscles (speech, eating and other oral functions)
Lateral view of the central nervous system of embryo at Carnegie stage 14 (Scale bar is 1 mm).

Week 8 - Stage 23

Stage23 MRI S01-vesicles.jpg


CNS ventricles
  • cavity within tube will form the contiguious space of the ventricules of the brain and central canal of spinal cord
  • this space is filled initially with amniotic fluid, later with CerebroSpinal Fluid (CSF)
  • CSF is secreted by a modified vascular structure, the chorioid plexus, lying within the ventricles

Links: Neural - Ventricular System Development)

Brain Flexures

Rapid growth folds the neural tube forming 3 brain flexures (cranial to caudal)

  • cephalic flexure - (mesencephalic) pushes mesencephalon upwards
  • pontine flexure - generates 4th ventricle
  • cervical flexure - between brain stem and spinal cord

Neural Layers

Human Embryo (Week 8, Stage 22) developing head section
Stage 22 developing cortex
Neuron and supporting glial cells
  • neural stem cells lie in the layer closest to the ventricular space, the ventricular layer
    • this layer generates both neuroblasts and glioblasts

Neuroblasts - neurons arise first as neuroblasts and migrate along radial gial, their migration stops at cortical plate. Glioblasts - glia arise later as glioblasts

Both neurons and glia undergo a complex process of growth, differentiation and interaction over a long developmental time period.

Spinal Cord Axes

    • Experimental manipulation of interactions.
    • Initial experiments looked at how isolated tissues may influence the development of the spinal cord.
    • Repositionining of specific tissues both in vivo and in vitro
    • specific markers of or alteration of differentiation.

Notocord Induction

    • Ventral- Sonic Hedgehog
    • notochord secretes sonic hedgehog
    • Gene expression studies (ISH) showed shh gene expression occured in a subset of inducing tissues
    • has a patterning role elsewhere (limb, sclerotome, lung)
    • 2 signaling activities acting (locally and at a distance) Ventral- Sonic Hedgehog
    • Binds to cell surface receptor patched
    • without shh, patched (Ptc) binds smoothened (Smo)
    • with shh shh-Ptc releases Smo activating G protein pathway

Early Development and Neural Derivatives

  • bilaminar embryo- hyoblast
  • trilaminar embryo then ectoderm layer, neural plate, neural groove, neural tube and neural crest
  • cranial expansion of neural tube- central nervous system
  • caudal remainder of neural tube- spinal cord
  • neural crest
  • dorsal root ganglia
  • parasympathetic / sympathetic ganglia.
  • ectodermal placodes- components of the special senses: otic placode (otocyst), nasal placode, lens placode

Links: Placodes

Neural tube and Genes: neural specification- Notch/Delta, patched receptor. Border- fibroblast growth factor (fgf), BMP (BMP4, msx1) Rostral border- Dlx5

Neural Tube Patterning

    • segmented along its length- Hox/Lim gene expression
    • ventral identity- sonic hedgehog, BMP7/chordin interaction
    • dorsal identity- dorsalin

Fetal Development

Human Fetus CRL240mm brain.jpg

Human Fetus (CRL 240mm) Brain (left dorsolateral view)

For more details see Neural System - Fetal


Fetal - Second Trimester

Brain ventricles and ganglia development 03.jpg Brain fissure development 02.jpg
Brain and Ventricular Development[8] Brain Fissure Development[8]

Third Trimester

Human Fetus (CRL 240mm) Brain

Three-dimensional magnetic resonance imaging and image-processing algorithms have been used to quantitate between 29-41 weeks volumes of: total brain, cerebral gray matter, unmyelinated white matter, myelinated, and cerebrospinal fluid (grey matter- mainly neuronal cell bodies; white matter- mainly neural processes and glia). A study of 78 premature and mature newborns showed that total brain tissue volume increased linearly over this period at a rate of 22 ml/week. Total grey matter also showed a linear increase in relative intracranial volume of approximately 1.4% or 15 ml/week. The rapid increase in total grey matter is mainly due to a fourfold increase in cortical grey matter. Quantification of extracerebral and intraventricular CSF was found to change only minimally.[9]

Thyroid System and Neural Development

Human thyroid system and neural development.jpg

Human thyroid system and neural development

Timeline of human thyroid system and brain development from conception to birth.[10] (Estimation of neurogenesis adapted from Bayer et al.[11])

Links: Endocrine - Thyroid Development

Gliogenesis and Myelination

Glial cells have many different types and roles in central and peripheral neural development, though they are typically described as "supportive", and have the same early embryonic origins as neurons. (More? [neuron7.htm Gliogenesis and Myelination])

Early in neural development a special type of developmental glia, radial glia, provide pathway for developing neuron (neuroblasts) migration out from the proliferating ventricular layer and are involved in the subsequent lamination and columnar organization of the central nervous system.

Types of glia: radial glia, astroglia, oligodendroglia, microglia and Schwann cells.

Gene Diseases - Sonic Hedgehog

SHH Human mutation- holoprosencephaly 3

  • characteristic facies of the severe form of HPE which included a single fused eye (cyclopia) and a nose-like structure (proboscis) above the eye
  • Downstream targets of Sonic hedgehog signalling: transcription factors like Gli3 (responsible for Greigs polycephalosyndactyly in humans), d Hoxd13 (responsible for polysyndactyly)


  1. Yang HJ, Lee DH, Lee YJ, Chi JG, Lee JY, Phi JH, Kim SK, Cho BK & Wang KC. (2014). Secondary neurulation of human embryos: morphological changes and the expression of neuronal antigens. Childs Nerv Syst , 30, 73-82. PMID: 23760472 DOI.
  2. Ozair MZ, Kintner C & Brivanlou AH. (2013). Neural induction and early patterning in vertebrates. Wiley Interdiscip Rev Dev Biol , 2, 479-98. PMID: 24014419 DOI.
  3. Ponti G, Obernier K, Guinto C, Jose L, Bonfanti L & Alvarez-Buylla A. (2013). Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice. Proc. Natl. Acad. Sci. U.S.A. , 110, E1045-54. PMID: 23431204 DOI.
  4. Pyrgaki C, Trainor P, Hadjantonakis AK & Niswander L. (2010). Dynamic imaging of mammalian neural tube closure. Dev. Biol. , 344, 941-7. PMID: 20558153 DOI.
  5. Massa V, Savery D, Ybot-Gonzalez P, Ferraro E, Rongvaux A, Cecconi F, Flavell R, Greene ND & Copp AJ. (2009). Apoptosis is not required for mammalian neural tube closure. Proc. Natl. Acad. Sci. U.S.A. , 106, 8233-8. PMID: 19420217 DOI.
  6. O'Rahilly R & Müller F. (1994). Neurulation in the normal human embryo. Ciba Found. Symp. , 181, 70-82; discussion 82-9. PMID: 8005032
  7. McShane SG, Molè MA, Savery D, Greene ND, Tam PP & Copp AJ. (2015). Cellular basis of neuroepithelial bending during mouse spinal neural tube closure. Dev. Biol. , 404, 113-24. PMID: 26079577 DOI.
  8. 8.0 8.1 Huang H, Xue R, Zhang J, Ren T, Richards LJ, Yarowsky P, Miller MI & Mori S. (2009). Anatomical characterization of human fetal brain development with diffusion tensor magnetic resonance imaging. J. Neurosci. , 29, 4263-73. PMID: 19339620 DOI.
  9. Hüppi PS, Warfield S, Kikinis R, Barnes PD, Zientara GP, Jolesz FA, Tsuji MK & Volpe JJ. (1998). Quantitative magnetic resonance imaging of brain development in premature and mature newborns. Ann. Neurol. , 43, 224-35. PMID: 9485064 DOI.
  10. Howdeshell KL. (2002). A model of the development of the brain as a construct of the thyroid system. Environ. Health Perspect. , 110 Suppl 3, 337-48. PMID: 12060827
  11. Bayer SA, Altman J, Russo RJ & Zhang X. (1993). Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology , 14, 83-144. PMID: 8361683


Online Textbooks

Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. Formation of the Neural Tube | Differentiation of the Neural Tube | Tissue Architecture of the Central Nervous System | Neuronal Types | Snapshot Summary: Central Nervous System and Epidermis

Neuroscience Purves, Dale; Augustine, George J.; Fitzpatrick, David; Katz, Lawrence C.; LaMantia, Anthony-Samuel; McNamara, James O.; Williams, S. Mark. Sunderland (MA): Sinauer Associates, Inc. ; c2001 Early Brain Development | Construction of Neural Circuits | Modification of Brain Circuits as a Result of Experience

Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. Neural Development | The three phases of neural development

Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct. Developmental Disorders Associated with Failure to Thrive

Search NLM Online Textbooks- "neural development" : Developmental Biology | The Cell- A molecular Approach | Molecular Biology of the Cell | Endocrinology


Hardwick LJ, Ali FR, Azzarelli R & Philpott A. (2015). Cell cycle regulation of proliferation versus differentiation in the central nervous system. Cell Tissue Res. , 359, 187-200. PMID: 24859217 DOI.

Götz M & Huttner WB. (2005). The cell biology of neurogenesis. Nat. Rev. Mol. Cell Biol. , 6, 777-88. PMID: 16314867 DOI.

Greene ND & Copp AJ. (2009). Development of the vertebrate central nervous system: formation of the neural tube. Prenat. Diagn. , 29, 303-11. PMID: 19206138 DOI.


Saitsu H & Shiota K. (2008). Involvement of the axially condensed tail bud mesenchyme in normal and abnormal human posterior neural tube development. Congenit Anom (Kyoto) , 48, 1-6. PMID: 18230116 DOI.

. (1970). Embryonic vertebrate central nervous system: revised terminology. The Boulder Committee. Anat. Rec. , 166, 257-61. PMID: 5414696 DOI.

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Search Pubmed: Neural System Development | Neural Development | Neural Tube Development | Spinal Cord Development

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Neural Terms  
Neural Development
  • 3DMRI - Three-dimensional magnetic resonance imaging. A new technique that allows 3D analysis of embryonic structures. (More? Magnetic Resonance Imaging)
  • 3rd ventricle - a fluid-filled space formed from neural tube lumen, located within the diencephalon (from the primary vesicle prosencephalon, forebrain).
  • 4th ventricle - a fluid-filled space formed from neural tube lumen, located within the rhombencephalon (from the primary vesicle, hindbrain).
  • adenohypophysis - (anterior pituitary) = 3 parts pars distalis, pars intermedia, pars tuberalis.
  • alar plate - afferent, dorsal horns
  • anlage - (German = primordium, structure or cells which will form a future structure.
  • arachnoid - (G.) spider web-like used in reference to the middle layer of the brain meninges, the arachnoid mater.
  • astrocytes - cells named by their "star-like" branching appearance, are the most abundant glial cells in the brain, important for the blood-brain barrier.
  • basal ganglia - (basal nuclei) neural structure derived from the secondary vesicle telencephalon (endbrain) structure from the earlier primary vesicle prosencephalon (forebrain)
  • basal plate - efferent, ventral horns
  • brachial plexus - mixed spinal nerves innervating the upper limb form a complex meshwork (crossing).
  • brain - general term for the central nervous system formed from 3 primary vesicles.
  • buccopharyngeal membrane - (oral membrane) at cranial (mouth) end of gastrointestinal tract (GIT) where surface ectoderm and GIT endoderm meet. (see also cloacal membrane)
  • cauda equina - (horse's tail) caudal extension of the mature spinal cord.
  • central canal - lumen, cavity of neural tube within the spinal cord. Space is continuous with ventricular system of the brain.
  • cerebral aqueduct - ventricular cavity within the mesencephalon.
  • cervical flexure - most caudal brain flexure (of 3) between spinal cord and rhompencephalon.
  • choroid plexus - specialized vascular plexus responsible for secreting ventricular fluid that with further additions becomes cerebrospinal fluid (CSF).
  • cloacal membrane - at caudal (anal) end of gastrointestinal tract (GIT) where surface ectoderm and GIT endoderm meet forms the openings for GIT, urinary, reproductive tracts. (see also buccopharyngeal membrane)
  • cortex - - CNS structure derived from the secondary vesicle telencephalon (endbrain) from the earlier primary vesicle prosencephalon (forebrain).
  • cortical plate - outer neural tube region which post-mitotic neuroblasts migrate too along radial glia to form adult cortical layers.
  • cranial flexure - (=midbrain flexure) most cranial brain flexure (of 3) between mesencephalon and prosencephalon.
  • diencephalon - the caudal portion of forebrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). (cavity- 3rd ventricle) Forms the thalmus and other nuclei in the adult brain. (sc-My-Met-Mes-Di-Tel)
  • dorsal root ganglia - (spinal ganglia) sensory ganglia derived from the neural crest lying laterally paired and dorsally to the spinal cord (in the embryo found ventral to the spinal cord). Connects centrally with the dorsal horn of the spinal cord.
  • dura mater- "tough" (Latin, mater = mother)
  • ectoderm - the germ layer which form the nervous system from the neural tube and neural crest.
  • ependyma - epithelia of remnant cells after neurons and glia have been generated and left the ventricular zone
  • floorplate - early forming thin region of neural tube closest to the notochord.
  • ganglia - (pl. of ganglion) specialized neural cluster.
  • glia - supporting, non-neuronal cells of the nervous system. Generated from neuroepithelial stem cells in ventricular zone of neural tube. Form astrocytes, oligodendrocytes.
  • grey matter - neural regions containing cell bodies (somas) of neurons. In the brain it is the outer layer, in the spinal cord it is inner layer. (see white matter white matter)
  • growth factor - usually a protein or peptide that will bind a cell membrane receptor and then activates an intracellular signaling pathway. The function of the pathway will be to alter the cell directly or indirectly by changing gene expression. (eg shh)
  • hox - (homeobox) family of transcription factors that bind DNA and activate gene expression. Expression of different Hox genes along neural tube defines rostral-caudal axis and segmental levels.
  • hydrocephalus - abnormality as the result of an imbalance between the rate at which the CSF is being formed and the rate at which the CSF is passing through the arachnoidal villi back into the blood (hydrocephalus rate is a function of the degree of imbalance in these two). Very small imbalance exhibit subtle, if any, symptoms. Large imbalances will have rapidly evolving symptoms of unmistakable import.
  • isthmus- (G. narrow passage)
  • lamina terminalis - anterior region of brain where cranial neuropore closes.
  • lumbar plexus - mixed spinal nerves innervating the lower limb form a complex meshwork (crossing).
  • mantle layer - layer of cells generated by first neuroblasts migrating from the ventricular zone of the neural tube. Layers are rearranged during development of the brain and spinal cord. (Ven-Man-Mar-CP)
  • marginal zone - layer of processes from neuroblasts in mantle layer. (Ven-Man-Mar-CP)
  • mater - (Latin, mater = mother)
  • meninges - mesenchyme surrounding neural tube forms 3 layer (Dura-, pia-, arachnoid- mater) connective tissue sheath of nervous system. (D-P-A-cns)
  • mesencephalon - (midbrain), the middle portion of the 3 primary vesicle brain (week 4). (sc-R-M-P)
  • metencephalon - the cranial portion of hindbrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). Forms the pons and cerebellum in the adult brain. (sc-My-Met-Mes-Di-Tel)
  • microglia - CNS innate immune cells that have a macrophage function, derive from you sac progenitor cells migrating into the CNS. microglia
  • myelencephalon - the caudal portion of hindbrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). Forms the medulla in the adult brain. (sc-My-Met-Mes-Di-Tel)
  • neural tube - neural plate region of ectoderm pinched off to form hollow ectodermal tube above notochord in mesoderm.
  • neural tube defect - (NTD) any developmental abnormality that affects neural tube development. Commonly failure of neural tube closure.
  • neuroblast - undifferentiated neuron found in ventricular layer of neural tube.
  • neurohypophysis - (posterior pituitary=pas nervosa)
  • neuromere - term used to describe the segmental region of the neural tube.
  • neuron - The cellur "unit" of the nervous system, transmitting signals between neurons and other cells. The post-mitotic cells generated from neuroepithelial stem cells (neuroblasts) in ventricular zone of neural tube.
  • neuropore - opening at either end of neural tube cranial (rostral, anterior) neuropore closes (day 25) about 2 days before caudal (posterior) that closes at somite level 32 to 34. Neural Tube Defects (NTDs) can be due to failure of these two neuropores to close.
  • notochord - rod of cells lying in mesoderm layer ventral to the neural tube, induces neural tube and secretes sonic hedgehog which "ventralizes" the neural tube.
  • olfactory bulb - (cranial nerve I, CN I) bipolar neurons from nasal epithelium project axons through cribiform palate into olfactory bulb of the brain.
  • optic nerve - (cranial nerve II, CN II) retinal ganglion neurons project from the retina as a tract into the brain (at the level of the diencephalon).
  • optic vesicle - diencephalon outgrowth that forms the primordia of the retina of the eye.
  • otocyst - (otic vesicle) sensory [#placode placode] which sinks into mesoderm to form spherical vesicle (stage 13/14 embryo) that will form components of the inner ear.
  • pars - (L. part of)
  • pharyngeal arches - (branchial arches, Gk. gill) form structures of the head. Six arches form but only 4 form any structures. Each arch has a pouch, membrane and cleft.
  • pharynx - uppermost end of GIT, beginning at the buccopharyngeal membrane and at the level of the pharyngeal arches.
  • pia mater-
  • placode - specialized regions of ectoderm which form components of the sensory apparatus.
  • pontine flexure - middle brain flexure (of 3) between cervical and cranial flexure in opposite direction, also generates thin roof of rhombencephalon and divides it into myelencephalon and metencephalon. ( sc-^V^ )
  • prosencephalon - (forebrain), the most cranial portion of the 3 primary vesicle brain (week 4). (sc-R-M-P)
  • Rathke's pouch - a portion of the roof of the pharynx pushes upward towards the floor of the brain forming the anterior pituirary (adenohypophysis, pars distalis, pars tuberalis pars intermedia). Where it meets a portion of the brain pushing downward forming the posterior pituitary (neurohypophysis, pars nervosa). Rathke's pouch eventually looses its connection with the pharynx. (Martin Heinrich Rathke 1973-1860, embryologist and anatomist)
  • rhombencephalon - (hindbrain), the most caudal portion of the 3 primary vesicle brain (week 4). (sc-R-M-P)
  • rhombic lip - metencephalon posterior part extending from the roof of the fourth ventricle to dorsal neuroepithelial cells that contributes to the cerebellum.
  • roofplate - early forming thin region of neural tube closest to the overlying ectoderm.
  • spinal cord - caudal end of neural tube that does not contribute to brain. Note: the process of secondary neuralation contributes the caudal end of the spinal cord.
  • spinal ganglia - (dorsal root ganglia, drg) sensory ganglia derived from the neural crest lying laterally paired and dorsally to the spinal cord (in the embryo found ventral to the spinal cord). Connects centrally with the dorsal horn of the spinal cord.
  • spinal nerve - mixed nerve (motor and sensory) arising as latera pairs at each vertebral segmental level.
  • sonic hedgehog - (shh) secreted growth factor that binds patched (ptc) receptor on cell membrane. SHH function is different for different tissues in the embryo. In the nervous system, it is secreted by the notochord, ventralizes the neural tube, inducing the floor plate and motor neurons.
  • sulcus - (L. furrow) groove
  • sulcus limitans - longitudinal lateral groove in neural tube approx. midway between roofplate and floorplate. Groove divides alar (dorsal) and basal (ventral) plate regions.
  • sympathetic ganglia-
  • telencephalon - the cranial portion of forebrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). (cavity- lateral ventricles and some of 3rd ventricle) Forms the cerebral hemispheres in the adult brain. (sc-My-Met-Mes-Di-Tel)
  • thalamus - (G. thalamos= bedchamber) cns nucleus, lateral to 3rd ventricle, paired (pl thalami).
  • thyroid hormone - hormone required for brain development. T3 (3,5,3′-triiodothyronine) binding to nuclear receptors then act as a transcription factor in both neurons and glial cells.
  • transcription factor - a factor (protein or protein with steroid) that binds to DNA to alter gene expression, usually to activate. (eg steroid hormone+receptor, Retinoic acid+Receptor, Hox, Pax, Lim, Nkx-2.2)
  • trigeminal ganglion - (cranial nerve V, CN V) first arch ganglion, very large and has 3 portions.
  • vagal ganglion- (cranial nerve X, CN X) fourth and sixth arch ganglion, innervates the viscera and heart.
  • ventricles - the fluid-filled interconnected cavity system with the brain. Fluid (cerebrospinal fluid, CSF) is generated by the specialized vascular network, the choroid plexus. The ventricles are directly connected to the spinal canal (within the spinal cord).
  • ventricular zone - Neuroepithelial cell layer of neural tube closest to lumen. Neuroepithelial cells generate neurons, glia and ependymal cells. (Ven-Man-Mar-CP)
  • vestibulocochlear nerve - (cranial nerve VIII, CN VIII, also called statoacoustic)
  • white matter - - neural regions containing processes (axons) of neurons. In the brain it is the inner layer, in the spinal cord it is outer layer. (see grey matter)
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Additional Images

Historic Images

Bartelmez GW. The subdivisions of the neural folds in man. (1923) J. Comp. Neural., 35: 231-247.

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Cite this page: Hill, M.A. (2018, February 22) Embryology Neural System Development. Retrieved from

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