Neural - Diencephalon Development

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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 other notes sections.

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 | diencephalon | epithalamus | thalamus | hypothalamus‎ | pituitary | pineal | mesencephalon | tectum | rhombencephalon | metencephalon | pons | cerebellum | myelencephalon | medulla oblongata | spinal cord | neural vascular | ventricular | lateral ventricles | third ventricle | cerebral aqueduct | fourth ventricle | central canal | meninges | Category:Ventricular System | Category:Neural

Historic Embryology: 1912 Diencephalon

Historic Neural Embryology  
1883 Nervous System | 1893 Brain Structure | 1892 Nervous System Development | 1900 fourth ventricle | 1905 Brain Blood-Vessels | 1909 corpus ponto-bulbare | 1912 nuclei pontis - nucleus arcuatus | 1912 Diencephalon | 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 | 1934 Anencephaly | 1937 Anencephaly | 1945 Spinal Cord | 1945 cerebral cortex | Santiago Ramón y Cajal | Ziegler Neural Models | Historic Embryology Papers | Historic Disclaimer

Some Recent Findings

Mouse diencephalon territories
Mouse E10.5 diencephalon territories[1]
  • Barhl2 Determines the Early Patterning of the Diencephalon by Regulating Shh[2] "The diencephalon is the primary relay network transmitting sensory information to the anterior forebrain. During development, distinct progenitor domains in the diencephalon give rise to the pretectum (p1), the thalamus and epithalamus (p2), and the prethalamus (p3), respectively. Shh plays a significant role in establishing the progenitor domains. However, the upstream events influencing the expression of Shh are largely unknown. Here, we show that Barhl2 homeobox gene is expressed in the p1 and p2 progenitor domains and the in zona limitans intrathalamica (ZLI) and regulates the acquisition of identity of progenitor cells in the developing diencephalon. Targeted deletion of Barhl2 results in the ablation of Shh expression in the dorsal portion of ZLI and causes thalamic p2 progenitors to take the fate of p1 progenitors and form pretectal neurons. Moreover, loss of Barhl2 leads to the absence of thalamocortical axon projections, the loss of habenular afferents and efferents, and a gross diminution of the pineal gland. Thus, by acting upstream of Shh signaling pathway, Barhl2 plays a crucial role in patterning the progenitor domains and establishing the positional identities of progenitor cells in the diencephalon."

More recent papers  
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.

  • This search now requires a manual link as the original PubMed extension has been disabled.
  • The displayed list of references do not reflect any editorial selection of material based on content or relevance.
  • References also appear on 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.

More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Diencephalon Development | Diencephalon Embryology

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.

  • Autotaxin controls caudal diencephalon-mesencephalon development in the chick[3] "The diencephalon is the embryonic anlagen of the higher integration centers of the brain. Recent studies have elucidated how the cells in the rostral diencephalon acquire their regional identities. However, the understanding of the mechanisms under which the caudal diencephalon is formed is still limited. Here we focus on the role of Autotaxin (ATX), a lysophospholipid-generating exoenzyme, whose mRNA is detected in the caudal diencephalon. RNA interference against ATX altered the expression pattern of Pax6-regualted genes, Tcf4, Lim1, and En1, implying that ATX is required for the maintenance of the regional identity of the caudal diencephalon and the diencephalon-mesencephalon boundary (DMB). Furthermore, ATX-RNAi inhibited neuroepithelial cell proliferation on both sides of the DMB. We propose a dual role of ATX in chick brain development, in which ATX not only contributes to the formation of caudal diencephalon as a short-range signal, but also regulates the growth of mesencephalon as a long-range signal."

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

prosencephalon (forebrain) telencephalon Rhinencephalon, Amygdala, hippocampus, cerebrum (cortex), hypothalamus‎, pituitary | Basal Ganglia, lateral ventricles
diencephalon epithalamus, thalamus, Subthalamus, pineal, posterior commissure, pretectum, third ventricle
mesencephalon (midbrain) mesencephalon tectum, Cerebral peduncle, cerebral aqueduct, pons
rhombencephalon (hindbrain) metencephalon cerebellum
myelencephalon medulla oblongata, isthmus
spinal cord, pyramidal decussation, central canal

Early Brain Vesicles

Primary Vesicles

CNS primary vesicles.jpg

Secondary Vesicles

CNS secondary vesicles.jpg


  1. Martinez-Ferre A & Martinez S. (2012). Molecular regionalization of the diencephalon. Front Neurosci , 6, 73. PMID: 22654731 DOI.
  2. Ding Q, Balasubramanian R, Zheng D, Liang G & Gan L. (2017). Barhl2 Determines the Early Patterning of the Diencephalon by Regulating Shh. Mol. Neurobiol. , 54, 4414-4420. PMID: 27349434 DOI.
  3. Ohuchi H, Fukui H, Matsuyo A, Tomonari S, Tanaka M, Arai H, Noji S & Aoki J. (2010). Autotaxin controls caudal diencephalon-mesencephalon development in the chick. Dev. Dyn. , 239, 2647-58. PMID: 20737506 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.


Martinez-Ferre A & Martinez S. (2012). Molecular regionalization of the diencephalon. Front Neurosci , 6, 73. PMID: 22654731 DOI.

García-Moreno F, Pedraza M, Di Giovannantonio LG, Di Salvio M, López-Mascaraque L, Simeone A & De Carlos JA. (2010). A neuronal migratory pathway crossing from diencephalon to telencephalon populates amygdala nuclei. Nat. Neurosci. , 13, 680-9. PMID: 20495559 DOI.

Trujillo CM, Alonso A, Delgado AC & Damas C. (2005). The rostral and caudal boundaries of the diencephalon. Brain Res. Brain Res. Rev. , 49, 202-10. PMID: 16111550 DOI.

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Search Pubmed: Diencephalon Embryology | Diencephalon Development |

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Cite this page: Hill, M.A. (2024, June 22) Embryology Neural - Diencephalon Development. Retrieved from

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