Difference between revisions of "Neural - Ventricular System Development"

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Human- ventricular system cartoon.jpg


The ventricular system develops from the single cavity formed from the hollow neural tube. This fluid-filled space is separated from the amnion following fusion of the neural tube and closure of neuropores. At different regions sites within the wall (floor of lateral ventricle and roof of the third and fourth ventricles) differentiate to form choroid plexus a modified vascular structure which will produce cerebrospinal fluid (CSF)

Human choroid plexus (stage 22)

In development and the space within the spinal cord (central canal) and the brain (ventricles) was derived from the same space within the neural tube. In the adult these 2 spaces remain connected containing the same CSF.

Early in development the cavity within the neural tube (which will form the ventricular space) is filled with amniotic fluid. As the brain and spinal cord grow, this fluid filled space makes up the majority of the nervous system (by volume). Upon closure of the neuropores and development of the embryonic vasculature, this fluid is then synthesized by the choroid plexus, a specialized vascular epithelium. In mammals, the choroid plexuses develop at four sites in the roof of the neural tube shortly after its closure, in the order fourth (IV), lateral, and third (III) ventricles.

The choroid plexuses form one region of the blood-brain barrier that regulates the brain's internal environment.

In the adult, the choroid plexus produces about two thirds of the CSF, the rest is produced by ventricular ependymal cells and cells lining the subarachnoid space. Normal CSF contains high amounts of salts, sugars and lipids and low amounts of protein (0.3-0.7 microg/microL), though there appears to be 60+ proteins as identified by 2D gel. Presence of some protein in the CSF can be indicative of disruption of or incomplete blood/brain barrier.

Links: hydrocephalus | Category:Ventricular System
Neural Links: ectoderm | neural | neural crest | ventricular | sensory | Stage 22 | gliogenesis | neural fetal | Medicine Lecture - Neural | Lecture - Ectoderm | Lecture - Neural Crest | Lab - Early Neural | neural abnormalities | folic acid | iodine deficiency | Fetal Alcohol Syndrome | neural postnatal | neural examination | Histology | Historic Neural | Category:Neural
Neural Parts: neural | prosencephalon | telencephalon cerebrum | amygdala | hippocampus | basal ganglia | lateral ventricles | diencephalon | Epithalamus | thalamus | hypothalamus‎ | pituitary | pineal | third ventricle | mesencephalon | tectum | cerebral aqueduct | rhombencephalon | metencephalon | pons | cerebellum | myelencephalon | medulla oblongata | spinal cord | neural vascular | meninges | Category:Neural
Historic Papers - Ventricular 

Heuser CH. The development of the cerebral ventricles in the pig. (1913) Amer. J Anat. 15(2): 215-.

Streeter GL. The development of the venous sinuses of the dura mater in the human embryo. (1915) Amer. J Anat.18: 145-178.

Weed LH. The development of the cerebro-spinal spaces in pig and in man. (1917) Contrib. Embryol., Carnegie Inst. Wash., 5, No. 14 .

Sensenig EC. The early development of the meninges of the spinal cord in human embryos. (1951) Contrib. Embryol., Carnegie Inst. Wash. Publ. 611,

Some Recent Findings

WHO - The global action report on preterm birth
WHO - The global action report on preterm birth
  • The cerebrospinal fluid Inflammatory Response to Preterm Birth[1] "preterm birth is the leading risk factor for perinatal white matter injury, which can lead to motor and neuropsychiatric impairment across the life course. There is an unmet clinical need for therapeutics. White matter injury is associated with an altered inflammatory response in the brain, primarily led by microglia, and subsequent hypomyelination. However, microglia can release both damaging and trophic factors in response to injury, and a comprehensive assessment of these factors in the preterm central nervous system (CNS) has not been carried out. Method: A custom antibody array was used to assess relative levels of 50 inflammation- and myelination-associated proteins in the cerebrospinal fluid (CSF) of preterm infants in comparison to term controls. Conclusion: Preterm CSF shows a distinct neuroinflammatory profile compared to term controls, suggestive of a complex neural environment with concurrent damaging and reparative signals. We propose that limitation of pro-inflammatory responses, which occur early after perinatal insult, may prevent expression of myelination-suppressive genes and support healthy white matter development." preterm birth
  • MafB is required for development of the hindbrain choroid plexus[2] "The choroid plexus (ChP) is a non-neural epithelial tissue that produces cerebrospinal fluid (CSF). The ChP differentiates from the roof plate, a dorsal midline structure of the neural tube. However, molecular mechanisms underlying ChP development are poorly understood compared to neural development. MafB is a bZip transcription factor that is known to be expressed in the roof plate. Here we investigated the role of MafB in embryonic development of the hindbrain ChP (hChP) using Mafb-deficient mice. ...Collectively, our findings reveal that MafB play an important role in promoting hChP development during embryogenesis."
  • Floor plate descendants in the ependyma of the adult mouse Central Nervous System[3] "During embryonic development of the Central Nervous System (CNS), the expression of the bHLH transcription factor Nato3 (Ferd3l) is unique and restricted to the floor plate of the neural tube. In mice lacking Nato3 the floor plate cells of the spinal cord do not fully mature, whereas in the midbrain floor plate, progenitors lose some neurogenic activity, giving rise to a reduced population of dopaminergic neurons. Since the floor plate is considered to be disintegrated at the time of birth, Nato3 expression was never tested postnatally and in adult mice. ...(Nato3 KO) Taken together, Nato3 defines an unrecognized subpopulation of medial cells positioned at only one side of circular ependymal structures, and it may affect their regulatory activities and neuronal stem cell function."
More recent papers  
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More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Neural Ventricular System Development | Choroid Plexus Development | Cerebrospinal fluid Development | hydrocephalus | Subarachnoid Space Development

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.

  • Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton regulation in hydrocephalus pathology[4] "Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi-ciliated ependymal cells through the ventricular system of the vertebrate brain. Defects in the ependymal layer functionality are a common cause of hydrocephalus. N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulator of actin cytoskeleton and N-WASP knockout caused embryonic lethality in mice with neural tube and cardiac abnormalities. ... Taken together, our results suggest that N-WASP plays a critical role in normal brain development and implicate actin cytoskeleton regulation as a vulnerable axis frequently deregulated in hydrocephalus." hydrocephalus

Development Overview

The initial neural grove and tube, with open neuropores, is filled with amniotic fluid. By stage 13 (4 weeks, GA week 6) the neuropores are closed and the neural tube is no longer directly connected to the amniotic cavity. Initially during early 3 and 5 vesicle neural stages and prior to choroid plexus development, the "ventricular space" is reliant upon overall tube growth and directional fluid transport to maintain the fluid-filled space. There is research suggesting that hydrostatic pressure[5] and a functioning heart are required to maintain the vesicle spaces, and there are several models as to how pressure and osmotic gradients may be established. See also zebrafish model studies[6] and a recent review.[7]

Ventricular Timeline

Human Embryo (week 8, Stage 22) ventricular system
Human Fetus (week 10) showing choroid plexus and early ventricular system
Human Embryonic Ventricular Timeline
Week Carnegie Stage Event
Week 4 11 appearance of the optic ventricle. The neural groove/tube space is initially filled with amniotic fluid.
12 closure of the caudal neuropore, onset of the ventricular system and separates the ependymal from the amniotic fluid.
13 cavity of the telencephalon medium is visible.
Week 5 14 cerebral hemispheres and lateral ventricles begin, rhomboid fossa becomes apparent.
15 medial and lateral ventricular eminences cause indentations in the lateral ventricle
Week 6 16 hypothalamic sulcus is evident.
17 - 18 interventricular foramina are becoming relatively smaller, and cellular accumulations indicate the future choroid villi of the fourth and lateral ventricles.
Week 7 18 areae membranaceae rostralis and caudalis are visible in the roof of the fourth ventricle, and the paraphysis is appearing.
19 choroid villi are visible in the fourth ventricle, and a mesencephalic evagination (blindsack) is visible
Week 8 20 choroid villi are visible in the lateral ventricle.
21 olfactory ventricle is visible.
21 - 23 lateral ventricle has become C-shaped (anterior and inferior horns visible). Recesses develop in the third ventricle (optic, infundibular, pineal).
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
Links: ventricular | neural | timeline | Category:Timeline     Table Data Reference[8]


Fetal Period - posterior horn of the lateral ventricle, choroid plexus of the third ventricle, suprapineal recess, interthalamic adhesion, aqueduct, and apertures in the roof of the fourth ventricle.

Brain ventricles and ganglia development 03.jpg

Choroid Plexus

The choroid plexus along with ventricular ependymal cells and cells lining the subarachnoid space synthesise CSF. In humans, the choroid plexuses develop at four sites in the roof of the neural tube shortly after its closure, in the order fourth (IV), lateral, and third (III) ventricles.

Human- ventricular system cartoon.jpg Human Ventricular System

A schematic diagram of structures and specialized cell types bordering the different parts of the mammalian ventricular system, and in contact with the cerebrospinal fluid (CSF)[9]


  • CO - caudal opening of the central canal of the spinal cord
  • H - hypothalamic CSF-contacting neurons
  • HY - Hypophysis
  • LV - lateral ventricle
  • ME - median eminence
  • O - vascular organ of the terminal lamina
  • PIN - pineal organ
  • R - raphe nuclei
  • RET - retina
  • RF - Reissner's fiber
  • SE - septal region
  • SCO - subcommissural organ
  • SP - medullo-spinal CSF-contacting neurons
  • TEL - telencephalon
  • TF - terminal filum

Epithelium from the neural tube epithelium.

Mesenchyma from the meninges.

Enzymes required for CSF production are Na+/K+ ATPase and carbonic anhydrase.

Subarachnoid Space Development

  • Stage 14 (33 days) - initially as irregular spaces on the ventral surface of the spinal cord.
  • Stage 18 (44 days) - dura mater is formed and spaces surround the circumference of the spinal cord, which coalesce and contain many blood vessels.

Data from Patelska-Banaszewska M, Wozniak W. (2005)[10]

CSF Synthesis

Two key enzymes are required to produce CSF they are the Na+/K+ ATPase and carbonic anhydrase.

Other known chorid plexus enzymes include: alkaline and acid phosphatases, magnesium-dependent ATPase, glucose-6-phosphatase, thiamine pyrophosphatase, adenylate cyclase, oxidoreductase, esterases, hydrolases, cathepsin D, and glutathion S-transferase. (More? Catala M., 1998)

"The epithelial cells of the choroid plexus secrete cerebrospinal fluid (CSF), by a process that involves the movement of Na(+), Cl(-) and HCO(3)(-) from the blood to the ventricles of the brain. This creates the osmotic gradient, which drives the secretion of H(2)O. The unidirectional movement of the ions is achieved due to the polarity of the epithelium, i.e., the ion transport proteins in the blood-facing (basolateral) are different to those in the ventricular (apical) membranes."[11]

CSF Reabsorption

Arachnoid Granulation (image: Gray's Anatomy)

CSF drainage (absorption or reabsorption) into the venous system is through arachnoid granulations.

CSF in the subarachnoid space extends into the arachnoid granulations, which then project through the dura into the superior sagittal sinus.

See also note in CSF Circulation section, point 3.

Adult CSF Normal Values

CNS ventricles

Lumbar CSF

  • Opening pressure: 50–200 mm H2O CSF
  • Color: Colorless
  • Turbidity: Crystal clear
  • Mononuclear cells: less than 5 / mm3
  • Polymorphonuclear leukocytes: 0
  • Total protein: 22–38 mg/dl Range 9–58 mg/dl (mean ± 2.0 SD)
  • Glucose: 60–80% of blood glucose

(Data from: Clinical Methods, 3rd ed, Table 74.1)

CSF Circulation

Ventricular space cartoon

Information below is for the adult and is based upon data from a radiologic investigation using MR imaging and radionuclide cisternography.[12]

  1. CSF-circulation is propelled by a pulsating flow, which causes an effective mixing. Flow is produced by the alternating pressure gradient, which is a consequence of the systolic expansion of the intracranial arteries causing expulsion of CSF into the compliant and contractable spinal subarachnoid space.
  2. No bulk flow is necessary to explain the transport of tracers in the subarachnoid space.
  3. Main absorption of the CSF is not through the Pacchionian granulations (arachnoid granulations), but a major part of the CSF transportation to the blood-stream is likely to occur via the paravascular and extracellular spaces of the central nervous system. (MH- Note this statement conflicts with previous CSF Reabsorption in literature)
  4. The intracranial dynamics may be regarded as the result of an interplay between the demands for space by the four components of the intracranial content (arterial blood, brain volume, venous blood and CSF).
  5. Interaction has a time offset within the cerebral hemispheres in a fronto-occipital direction during the cardiac cycle (the fronto-occipital "volume wave").
  6. Outflow from the cranial cavity to the cervical subarachnoid space (SAS) is dependent in size and timing on the intracranial arterial expansion during systole.


Dandy Walker Syndrome

Dandy Walker malformation (MRI)[13]

The vermis of the cerebellum can be small or absent, the fourth ventricle enlarges due to cyst formation.

An ultrasound study[14] of fetuses with Dandy-Walker malformation 13 to 16 weeks (GA 15-18 weeks) identified the fourth ventricle widely open posteriorly, even in the standard transcerebellar view, and the brainstem-vermis (BV) angle was > 45°, significantly increased compared to that in normal fetuses (P < 0.0001). Note that at this age, an open fourth ventricle can also found in about 10% of normal fetuses.

Links: Dandy-Walker | hydrocephalus | Genetics Home Reference


See hydrocephalus


  1. Boardman JP, Ireland G, Sullivan G, Pataky R, Fleiss B, Gressens P & Miron V. (2018). The Cerebrospinal Fluid Inflammatory Response to Preterm Birth. Front Physiol , 9, 1299. PMID: 30258368 DOI.
  2. Koshida R, Oishi H, Hamada M, Takei Y & Takahashi S. (2017). MafB is required for development of the hindbrain choroid plexus. Biochem. Biophys. Res. Commun. , 483, 288-293. PMID: 28025141 DOI.
  3. Khazanov S, Paz Y, Hefetz A, Gonzales BJ, Netser Y, Mansour AA & Ben-Arie N. (2017). Floor plate descendants in the ependyma of the adult mouse Central Nervous System. Int. J. Dev. Biol. , 61, 257-265. PMID: 27528042 DOI.
  4. Jain N, Lim LW, Tan WT, George B, Makeyev E & Thanabalu T. (2014). Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton regulation in hydrocephalus pathology. Exp. Neurol. , 254, 29-40. PMID: 24462670 DOI.
  5. Desmond ME, Levitan ML & Haas AR. (2005). Internal luminal pressure during early chick embryonic brain growth: descriptive and empirical observations. Anat Rec A Discov Mol Cell Evol Biol , 285, 737-47. PMID: 15977221 DOI.
  6. Schier AF, Neuhauss SC, Harvey M, Malicki J, Solnica-Krezel L, Stainier DY, Zwartkruis F, Abdelilah S, Stemple DL, Rangini Z, Yang H & Driever W. (1996). Mutations affecting the development of the embryonic zebrafish brain. Development , 123, 165-78. PMID: 9007238
  7. Gato A & Desmond ME. (2009). Why the embryo still matters: CSF and the neuroepithelium as interdependent regulators of embryonic brain growth, morphogenesis and histiogenesis. Dev. Biol. , 327, 263-72. PMID: 19154733 DOI.
  8. O'Rahilly R. and Müller F. Ventricular system and choroid plexuses of the human brain during the embryonic period proper. (1990) Amer. J Anat.189(4); 285-302 PMID 2285038
  9. Veening JG & Barendregt HP. (2010). The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review. Cerebrospinal Fluid Res , 7, 1. PMID: 20157443 DOI.
  10. Patelska-Banaszewska M & Woźniak W. (2005). The subarachnoid space develops early in the human embryonic period. Folia Morphol. (Warsz) , 64, 212-6. PMID: 16228957
  11. Speake T, Whitwell C, Kajita H, Majid A & Brown PD. (2001). Mechanisms of CSF secretion by the choroid plexus. Microsc. Res. Tech. , 52, 49-59. PMID: 11135448 <49::AID-JEMT7>3.0.CO;2-C DOI.
  12. Greitz D. (1993). Cerebrospinal fluid circulation and associated intracranial dynamics. A radiologic investigation using MR imaging and radionuclide cisternography. Acta Radiol Suppl , 386, 1-23. PMID: 8517189
  13. Saleem SN. (2014). Fetal MRI: An approach to practice: A review. J Adv Res , 5, 507-23. PMID: 25685519 DOI.
  14. Contro E, Volpe P, De Musso F, Muto B, Ghi T, De Robertis V & Pilu G. (2014). Open fourth ventricle prior to 20 weeks' gestation: a benign finding?. Ultrasound Obstet Gynecol , 43, 154-8. PMID: 24151160 DOI.


Online Textbooks


Gato A & Desmond ME. (2009). Why the embryo still matters: CSF and the neuroepithelium as interdependent regulators of embryonic brain growth, morphogenesis and histiogenesis. Dev. Biol. , 327, 263-72. PMID: 19154733 DOI.

Johansson PA, Dziegielewska KM, Liddelow SA & Saunders NR. (2008). The blood-CSF barrier explained: when development is not immaturity. Bioessays , 30, 237-48. PMID: 18293362 DOI.

Dziegielewska KM, Ek J, Habgood MD & Saunders NR. (2001). Development of the choroid plexus. Microsc. Res. Tech. , 52, 5-20. PMID: 11135444 <5::AID-JEMT3>3.0.CO;2-J DOI.

Catala M. (1998). Embryonic and fetal development of structures associated with the cerebro-spinal fluid in man and other species. Part I: The ventricular system, meninges and choroid plexuses. Arch. Anat. Cytol. Pathol. , 46, 153-69. PMID: 9754371


Desmond ME, Levitan ML & Haas AR. (2005). Internal luminal pressure during early chick embryonic brain growth: descriptive and empirical observations. Anat Rec A Discov Mol Cell Evol Biol , 285, 737-47. PMID: 15977221 DOI.

Patelska-Banaszewska M & Woźniak W. (2004). The development of the epidural space in human embryos. Folia Morphol. (Warsz) , 63, 273-9. PMID: 15478101

Shotland LI & Hecox KE. (1990). The effect of probe tube reference placement on sound pressure level variability. Ear Hear , 11, 306-9. PMID: 2210106

Oteruelo FT. (1986). On the cavum septi pellucidi and the cavum Vergae. Anat Anz , 162, 271-8. PMID: 3813041

Osaka K, Handa H, Matsumoto S & Yasuda M. (1980). Development of the cerebrospinal fluid pathway in the normal and abnormal human embryos. Childs Brain , 6, 26-38. PMID: 7351160

Osaka K, Matsumoto S & Yasuda M. (1977). [The development of cerebro-spinal fluid pathway in human embryos (author's transl)]. No Shinkei Geka , 5, 1047-55. PMID: 909616

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Additional Images


  • aqueduct of Sylvius - (cerebral aqueduct) acts as a tubular communication between the third and fourth ventricles.
  • cerebral aqueduct - (aqueduct of Sylvius) acts as a tubular communication between the third and fourth ventricles.
  • cerebrospinal fluid -
  • choroid plexus

Glossary Links

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Cite this page: Hill, M.A. (2020, January 18) Embryology Neural - Ventricular System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_-_Ventricular_System_Development

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