Neural - Meninges Development

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Human embryo meninges and developing brain. (Week 8, Carnegie stage 22)

The meninges (singular meninx; Greek, meninx = membrane) are a complex connective tissue surrounding the central nervous system (brain and spinal cord). The 3 layers from the central nervous outward are: pia mater, arachnoid mater, and the dura mater. All three layers form initially from the meninx primitiva, a meningeal mesenchyme. The pia mater and the arachnoid can together be called called leptomeninx, and dura mater the pachymeninx.

There have been many theories to the embryonic origins of the three layers that form the meninges, as well as potential differences between species. The safest term would be mesenchymal in origin, but the actual source of this mesenchyme may also differ in the same species at different levels of the central nervous system. The space under the arachnoid layer (subarachnoid space) is filled with cerebrospinal fluid.

Recent studies also suggest that rather than acting as a passive connective tissue "neural container" during development, the meninges may also interact and regulate cranial skull and neural development. In studying meninges development vascular, lymphatic and cerebrospinal fluid development should also be considered.

Historically, see the 1951 paper describing spinal cord meninges development.[1]

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Some Recent Findings

  • Review - The Tentorium Cerebelli[2] "The tentorium cerebelli functions as a partition, dispelling the burden of weight from supratentorial structures upon inferior brain matter. Clinicians and neurosurgeons, when assessing pathological findings, should have knowledge regarding the tentorium cerebelli anatomy. This work of literature is a comprehensive review of the tentorium cerebelli, including its anatomy, embryology, and clinical and surgical implications. The evolutionary pattern demonstrates sequential stages to higher mammalian lineage. An understanding of the complexity of the neurovascular structures and the anatomy of the tentorium cerebelli is crucial for surgical procedures by neurosurgeons."
  • Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain[3] "Properties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the "blood-brain barrier". These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules."
  • Postnatal development of lymphatic vasculature in the brain meninges[4] "Traditionally, the central nervous system (CNS) has been viewed as an immune-privileged environment with no lymphatic vessels. This view was partially overturned by the discovery of lymphatic vessels in the dural membrane that surrounds the brain, in contact with the interior surface of the skull. We here examine the distribution and developmental timing of these lymphatic vessels. ...We have found that between birth and postnatal day (P) 13, lymphatic vessels extend alongside dural blood vessels from the side of the skull toward the midline. Between P13 and P20, lymphatic vessels along the transverse sinuses reach the superior sagittal sinus (SSS) and extend along the SSS toward the olfactory bulb." Mouse Development
  • Intermediate filament protein nestin is expressed in developing meninges[5] " Nestin is a type VI intermediate filament protein known as a marker for progenitor cells that can be mostly found in tissues during the embryonic and fetal periods. ...In this study, in the human meninges intense nestin expression was detected as early as in the 9th week of development. Intensity of this expression gradually decreased in later stages of development and nestin expression still persisted in a small population of newborn meningeal cells."
More recent papers  
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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.

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Search term: Meninges Development

Ana C Londoño, Carlos A Mora Role of CXCL13 in the formation of the meningeal tertiary lymphoid organ in multiple sclerosis. F1000Res: 2018, 7;514 PubMed 30345018

Eloísa Herrera, Marta Agudo-Barriuso, Verónica Murcia-Belmonte Cranial Pair II: The Optic Nerves. Anat Rec (Hoboken): 2018; PubMed 30306726

David A Giles, Patrick C Duncker, Nicole M Wilkinson, Jesse M Washnock-Schmid, Benjamin M Segal CNS resident classical DCs play a critical role in CNS autoimmune disease. J. Clin. Invest.: 2018; PubMed 30226829

James R Goodman, Zachariah O Adham, Randall L Woltjer, Amanda W Lund, Jeffrey J Iliff Characterization of dural sinus-associated lymphatic vasculature in human Alzheimer's dementia subjects. Brain Behav. Immun.: 2018; PubMed 30055243

Joshua S Stoolman, Patrick C Duncker, Amanda K Huber, David A Giles, Jesse M Washnock-Schmid, Athena M Soulika, Benjamin M Segal An IFNγ/CXCL2 regulatory pathway determines lesion localization during EAE. J Neuroinflammation: 2018, 15(1);208 PubMed 30012158

Search term: Pia Development

Sasmita Panda, Durg Vijai Singh ##Title## Front Microbiol: 2018, 9;2687 PubMed 30487781

Qun Chen, Xiaotian Zhang, Yongmin Xiong, Chen Chen, Shemin Lv The CD25+/CD4+ T cell ratio and levels of CII, CIX and CXI antibodies in serum may serve as biomarkers of pristane-induced arthritis in rats and Rheumatoid Arthritis in humans. Comp. Biochem. Physiol. C Toxicol. Pharmacol.: 2018; PubMed 30472493

William E Clifton, Jonathan J Stone, Neeraj Kumar, Tomas Marek, Robert J Spinner Delayed myelopathy in patients with traumatic pre-ganglionic brachial plexus avulsion injuries. World Neurosurg: 2018; PubMed 30471442

Barbara Kot, Hubert Sytykiewicz, Iwona Sprawka ##Title## Int J Mol Sci: 2018, 19(11); PubMed 30404183

Chaigne Benjamin, Scirè Carlo Alberto, Talarico Rosaria, Alexander Tobias, Amoura Zahir, Avcin Tadej, Beretta Lorenzo, Doria Andrea, Guffroy Aurelien, Guimarães Vera, Hachulla Éric, Krieg Thomas, Launay David, Lepri Gemma, Moinzadeh Pia, Müller-Ladner Ulf, Rednic Simona, Rodrigues Ana, Tas Sander W, van Vollenhoven R F, Vieira Ana, Bombardieri Stefano, Fonseca João Eurico, Galetti Ilaria, Schneider Matthias, Smith Vanessa, Cutolo Maurizio, Mosca Marta, Fischer-Betz Rebecca Mixed connective tissue disease: state of the art on clinical practice guidelines. RMD Open: 2018, 4(Suppl 1);e000783 PubMed 30402271

Search term: Arachnoid Development

Laura V Sainz, Julian Zipfel, Susanne R Kerscher, Annette Weichselbaum, Andrea Bevot, Martin U Schuhmann Cerebro-venous hypertension: a frequent cause of so-called "external hydrocephalus" in infants. Childs Nerv Syst: 2018; PubMed 30474714

Thorbjørn Søren Rønn Jensen, Nina Andersen-Ranberg, Frantz Rom Poulsen, Bo Bergholt, Torben Hundsholt, Kåre Fugleholm [National guidelines for treatment of chronic subdural haematoma]. Ugeskr. Laeg.: 2018, 180(42); PubMed 30327087

Osman Tanriverdi, Uzay Erdogan, Canan Tanik, Ilhan Yilmaz, Omur Gunaldi, Huseyin Utku Adilay, Ayca Arslanhan, Metehan Eseoglu Impact of sorafenib on epidural fibrosis: An immunohistochemical study. World J Clin Cases: 2018, 6(9);249-258 PubMed 30211205

Mendel D Castle-Kirszbaum, Brent Uren, James King, Yi Yuen Wang, Tony Goldschlager Glimpse into Pathophysiology of Sellar Arachnoid Cysts. World Neurosurg: 2018, 119;381-383 PubMed 30149172

Julia Velz, Jorn Fierstra, Luca Regli, Menno Germans Spontaneous Spinal Subarachnoid Hemorrhage With Development Of An Arachnoid Cyst - A Case Report And Review Of The Literature. World Neurosurg: 2018; PubMed 30149166

Search term: Dura Development

Bianca M Dijkstra, Hanne-Rinck J R Jeltema, Schelto Kruijff, Rob J M Groen The application of fluorescence techniques in meningioma surgery-a review. Neurosurg Rev: 2018; PubMed 30519770

Ryota Kubo, Yoshiko Ariji, Tohru Taniguchi, Michihito Nozawa, Akitoshi Katsumata, Eiichiro Ariji Panoramic radiographic features that predict the development of bisphosphonate-related osteonecrosis of the jaw. Oral Radiol: 2018, 34(2);151-160 PubMed 30484130

Deborah Ferguson, Kevin Agyemang, Christopher Barrett, Calan Mathieson A low cost dural closure simulation model for tomorrow's spinal neurosurgeons. Br J Neurosurg: 2018;1-4 PubMed 30475077

Jin-Eon Han, Jin-Hwa Cho, Michiko Nakamura, Maan-Gee Lee, Il-Sung Jang ##Title## Korean J. Physiol. Pharmacol.: 2018, 22(6);649-660 PubMed 30402025

Cameron T Trueblood, Idiata W Iredia, Eileen Collyer, Veronica J Tom, Shaoping Hou The development of cardiovascular dysfunction in a rat spinal cord crush model and responses to serotonergic interventions. J. Neurotrauma: 2018; PubMed 30362884

Meninges simplified cartoon

Pia Mater

The pia mater forms innermost part of the meningial layers and is a fine connective tissue covering of the central nervous system. Lies beneath the arachnoid materand then tough outer dura mater layer. All three layers form from the meninx primitiva, a meningeal mesenchyme that is mesodermal and neural crest in origin. The space overlying the pia mater (subarachnoid space) is filled with cerebrospinal fluid. The pia mater has close contact with the spinal cord and brain, in the brain it follows down into the sulci and fissures of the cortex. This layer also fuses with the membranous lining of the ventricles (Template:Ependyma) forming the choroid plexus.

Arachnoid Mater

The arachnoid mater (Greek, arachne = spider + -oeides = form) forms the central part of the meninges layers as a meshwork (spider web-like) connective tissue covering of the central nervous system. Lying between the tough outer dura mater layer and the inner fine pia mater layer. All three layers form from the meninx primitiva, a meningeal mesenchyme that is mesodermal and neural crest in origin. The space underlying the arachnoid mater (subarachnoid space) is filled with cerebrospinal fluid.

Dura Mater

The dura mater (Latin, dura mater = hard mother) forms the outer tough connective tissue layer of the meninges 3 layers that cover the central nervous system. of 3 layers (overlays the arachnoid mater middle layer and pia mater inner layer). All three layers form from the meninx primitiva, a meningeal mesenchyme that is mesodermal and neural crest in origin.

At the level of the skull, the outer dura layer forms the inner periosteum of the skull and the inner dura layer forms the dural folds (falx and tentorium) that contains the dural sinuses. The dura mater also expresses osteogenic growth factors that may be required for ossification of cranial vault bones. At the level of the spinal cord, the dura is separated from the periosteum of the vertebral canal by an epidural space.

Dural Venous Sinuses

The dural venous sinuses form the major drainage of the brain to the internal jugular veins in the adult.

The dural venous sinuses:

  • lie between the dura mater layers (endosteal layer and meningeal)
  • run alone not parallel to arteries.
  • are valveless allowing for bidirectional blood flow

Unpaired - superior sagittal sinus, inferior sagittal sinus, straight sinus, occipital sinus, intercavernous sinus Paired - transverse sinus, sigmoid sinus, superior petrosal sinus, inferior petrosal sinus, cavernous sinus, sphenoparietal sinus, basilar venous plexus

The following figures are from a 1915 study of the venous sinuses of the dura mater in the human embryo.[6]

Cerebellar Tentorium

The cerebellar tentorium or tentorium cerebelli forms an extension of the dura mater separating the cerebellum from the inferior portion of the occipital lobes. For a recent review see.[2]


  1. Sensenig EC. The early development of the meninges of the spinal cord in human embryos. (1951) Contrib. Embryol., Carnegie Inst. Wash. Publ. 611,
  2. 2.0 2.1 Rai R, Iwanaga J, Shokouhi G, Oskouian RJ & Tubbs RS. (2018). The Tentorium Cerebelli: A Comprehensive Review Including Its Anatomy, Embryology, and Surgical Techniques. Cureus , 10, e3079. PMID: 30305987 DOI.
  3. Saunders NR, Dziegielewska KM, Møllgård K & Habgood MD. (2018). Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain. J. Physiol. (Lond.) , , . PMID: 29774535 DOI.
  4. Izen RM, Yamazaki T, Nishinaka-Arai Y, Hong YK & Mukouyama YS. (2018). Postnatal development of lymphatic vasculature in the brain meninges. Dev. Dyn. , , . PMID: 29493038 DOI.
  5. Yay A, Ozdamar S, Canoz O, Baran M, Tucer B & Sonmez MF. (2014). Intermediate filament protein nestin is expressed in developing meninges. Bratisl Lek Listy , 115, 718-22. PMID: 25428542
  6. Streeter GL. The development of the venous sinuses of the dura mater in the human embryo. (1915) Amer. J Anat.18: 145-178.


Weller RO, Sharp MM, Christodoulides M, Carare RO & Møllgård K. (2018). The meninges as barriers and facilitators for the movement of fluid, cells and pathogens related to the rodent and human CNS. Acta Neuropathol. , 135, 363-385. PMID: 29368214 DOI.

Mortazavi MM, Quadri SA, Khan MA, Gustin A, Suriya SS, Hassanzadeh T, Fahimdanesh KM, Adl FH, Fard SA, Taqi MA, Armstrong I, Martin BA & Tubbs RS. (2018). Subarachnoid Trabeculae: A Comprehensive Review of Their Embryology, Histology, Morphology, and Surgical Significance. World Neurosurg , 111, 279-290. PMID: 29269062 DOI.

Adeeb N, Mortazavi MM, Deep A, Griessenauer CJ, Watanabe K, Shoja MM, Loukas M & Tubbs RS. (2013). The pia mater: a comprehensive review of literature. Childs Nerv Syst , 29, 1803-10. PMID: 23381008 DOI.

Adeeb N, Mortazavi MM, Tubbs RS & Cohen-Gadol AA. (2012). The cranial dura mater: a review of its history, embryology, and anatomy. Childs Nerv Syst , 28, 827-37. PMID: 22526439 DOI.

Siegenthaler JA & Pleasure SJ. (2011). We have got you 'covered': how the meninges control brain development. Curr. Opin. Genet. Dev. , 21, 249-55. PMID: 21251809 DOI.

Patel N & Kirmi O. (2009). Anatomy and imaging of the normal meninges. Semin. Ultrasound CT MR , 30, 559-64. PMID: 20099639

Mack J, Squier W & Eastman JT. (2009). Anatomy and development of the meninges: implications for subdural collections and CSF circulation. Pediatr Radiol , 39, 200-10. PMID: 19165479 DOI.

O'Rahilly R & Müller F. (1986). The meninges in human development. J. Neuropathol. Exp. Neurol. , 45, 588-608. PMID: 3746345


Tanaka M. (2016). Embryological Consideration of Dural Arteriovenous Fistulas. Neurol. Med. Chir. (Tokyo) , 56, 544-51. PMID: 27250699 DOI.

Yokogawa N, Murakami H, Demura S, Kato S, Yoshioka K, Yamamoto M, Iseki S & Tsuchiya H. (2015). Effects of Radiation on Spinal Dura Mater and Surrounding Tissue in Mice. PLoS ONE , 10, e0133806. PMID: 26214850 DOI.

Baltsavias G, Parthasarathi V, Aydin E, Al Schameri RA, Roth P & Valavanis A. (2015). Cranial dural arteriovenous shunts. Part 1. Anatomy and embryology of the bridging and emissary veins. Neurosurg Rev , 38, 253-63; discussion 263-4. PMID: 25468011 DOI.

Tochitani S & Kondo S. (2013). Immunoreactivity for GABA, GAD65, GAD67 and Bestrophin-1 in the meninges and the choroid plexus: implications for non-neuronal sources for GABA in the developing mouse brain. PLoS ONE , 8, e56901. PMID: 23437266 DOI.

Search PubMed

Search Pubmed: Development Meninges Development


Salvi G. Meninges histogenesis and structure (L'istogenesi E La Struttura Delle Meningi). (1898) Thèse de Paris.

Harvey SC. and Burr HS. An experimental study of the origin of the meninges. (1924) Proc. Soc. Exper. Biol. and Med. 22: 52-53.

Harvey SC. and Burr HS. The development of the meninges. (1926) Arch Neurol Psychiatry 15:545–567

O'Rahilly R. and Müller F. The meninges in human development. (1986) J Neuropathol Exp Neurol 45: 588–608.

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


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