Neural - Telencephalon 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

Some Recent Findings

  • SHH signaling mediated by a prechordal and brain enhancer controls forebrain organization[1] "sonic hedgehog (SHH) signaling plays a pivotal role in 2 different phases during brain development. Early SHH signaling derived from the prechordal plate (PrCP) triggers secondary Shh induction in the forebrain, which overlies the PrCP, and the induced SHH signaling, in turn, directs late neuronal differentiation of the forebrain. Consequently, Shh regulation in the PrCP is crucial for initiation of forebrain development. However, no enhancer that regulates prechordal Shh expression has yet been found. Here, we identified a prechordal enhancer, named SBE7, in the vicinity of a cluster of known forebrain enhancers for Shh This enhancer also directs Shh expression in the ventral midline of the forebrain, which receives the prechordal SHH signal. Thus, the identified enhancer acts not only for the initiation of Shh regulation in the PrCP but also for subsequent Shh induction in the forebrain. Indeed, removal of the enhancer from the mouse genome markedly down-regulated the expression of Shh in the rostral domains of the axial mesoderm and in the ventral midline of the forebrain and hypothalamus‎ in the mouse embryo, and caused a craniofacial abnormality similar to human holoprosencephaly (HPE). These findings demonstrate that SHH signaling mediated by the newly identified enhancer is essential for development and growth of the ventral midline of the forebrain and hypothalamus. Understanding of the Shh regulation governed by this prechordal and brain enhancer provides an insight into the mechanism underlying craniofacial morphogenesis and the etiology of HPE.
  • LDB1 Is Required for the Early Development of the Dorsal telencephalon and the thalamus[2] "LIM domain binding protein 1 (LDB1) is a protein cofactor that participates in several multiprotein complexes with transcription factors that regulate mouse forebrain development. Since Ldb1 null mutants display early embryonic lethality, we used a conditional knockout strategy to examine the role of LDB1 in early forebrain development using multiple Cre lines. Loss of Ldb1 from E8.75 using Foxg1Cre caused a disruption of midline boundary structures in the dorsal telencephalon. While this Cre line gave the expected pattern of recombination of the floxed Ldb1 locus, unexpectedly, standard Cre lines that act from embryonic day (E)10.5 (Emx1Cre) and E11.5 (NesCre) did not show efficient or complete recombination in the dorsal telencephalon by E12.5. Intriguingly, this effect was specific to the Ldb1 floxed allele, since three other lines including floxed Ai9 and mTmG reporters, and a floxed Lhx2 line, each displayed the expected spatial patterns of recombination. Furthermore, the incomplete recombination of the floxed Ldb1 locus using NesCre was limited to the dorsal telencephalon, while the ventral telencephalon and the diencephalon displayed the expected loss of Ldb1. This permitted us to examine the requirement for LDB1 in the development of the thalamus in a context wherein the cortex continued to express Ldb1. We report that the somatosensory VB nucleus is profoundly shrunken upon loss of LDB1. Our findings highlight the unusual nature of the Ldb1 locus in terms of recombination efficiency, and also report a novel role for LDB1 during the development of the thalamus."

More recent papers  
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  • The displayed list of references do not reflect any editorial selection of material based on content or relevance.
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More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Telencephalon Development | Telencephalon Embryology | Forebrain Development | Embryology Forebrain 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.

  • The Mammalian DM Domain Transcription Factor Dmrta2 Is Required for Early Embryonic Development of the Cerebral Cortex[3]"Development of the mammalian telencephalon is precisely organized by a combination of extracellular signaling events derived from signaling centers and transcription factor networks. Using gene expression profiling of the developing mouse dorsal telencephalon, we found that the DM domain transcription factor Dmrta2 (doublesex and mab-3-related transcription factor a2) is involved in the development of the dorsal telencephalon."
  • The transcription factor Foxg1 regulates telencephalic progenitor proliferationPubmedParser error: The PubmedParser extension received invalid XML data. () "The transcription factor Foxg1 is an important regulator of telencephalic cell cycles. Its inactivation causes premature lengthening of telencephalic progenitor cell cycles and increased neurogenic divisions, leading to severe hypoplasia of the telencephalon. ....We conclude that Foxg1 exerts control over telencephalic progenitor proliferation by cell autonomous mechanisms that include the regulation of Pax6, which itself is known to regulate proliferation cell autonomously in a regional manner."
  • Populations of subplate and interstitial neurons in fetal and adult human telencephalon[4] "In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata."
  • Ephrins guide migrating cortical interneurons in the basal telencephalon[5] "Cortical interneurons are born in the proliferative zones of the ganglionic eminences in the subpallium and migrate to the developing cortex along well-defined tangential routes. The mechanisms regulating interneuron migration are not completely understood. ... Together, these results suggest that ephrin-A3 acts as a repulsive cue that restricts cortical interneurons from entering inappropriate regions and thus contributes to define the migratory route of cortical interneurons."
  • FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation[6] "FoxG1 is a conserved transcriptional repressor that plays a key role in the specification, proliferation and differentiation of the telencephalon, and is expressed from the earliest stages of telencephalic development through to the adult. ...Knocking down either FoxG1 or TLE2 disrupts the development of the ventral telencephalon, supporting the idea that endogenous TLE2 and FoxG1 work together to specify the ventral telencephalon."

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

Adult Cerebral Cortex

Each lobe below is further divided into regions.

  • Frontal lobe
  • Parietal lobe
  • Occipital lobe
  • Temporal lobe
  • Limbic lobe
  • Insular cortex
  • Interlobar sulci/fissures

Early Brain Vesicles

Primary Vesicles

CNS primary vesicles.jpg

Secondary Vesicles

CNS secondary vesicles.jpg

Insular Cortex

(insula, insulary cortex, insular lobe) Region from the telencephalon forming part of the cerebral cortex located deep within the lateral fissure (Sylvian fissure) between the temporal lobe and the frontal lobe. Adult roles in consciousness, emotion, sensory and homeostasis, see review.[7]

  • less than 2% of total cortical surface area
  • receives afferents from some sensory thalamic nuclei
  • connected with amygdala and many limbic and association cortical areas

Historical Background  
  • 1928 Rose[8]
  • 1940 Brockhaus</ref>Brockhaus H. Die Cyto- und Myeloarchitektonik des Cortex claustralis und des Claustrum beim Menschen. (1940) Journal fuer Psychologie und Neurologie, 49:249–348.</ref>
  • 1985 Mesulam and Mufson[9]

Molecular Development

Regulatory Networks

Telencephalon gene regulatory network.jpg

Algorithm-based gene regulatory network structure for dorsal and ventral telencephalon development.[10]

To highlight the key regulators, the nodes representing genes predicted to be the parent of at least nine other genes are largest in size (Sox9, Mef2a, Elavl4 and Pou6f1), whereas those that are predicted to regulate at least five other genes are medium in size (Ngn2, Centg3, Tef, Tcf4, Wnt7b, Pou2f1, Yy1, Dll1, E2f1, Arx, and Creb).

Netrin-1 Signaling

Telencephalon- Netrin-1 signaling thalamocortical projections.jpg Model of the Role of Netrin-1 Signaling in the Topography of Thalamocortical Projections in the Ventral Telencephalon[11]

Models summarizing previous[12] and above reference[11] findings regarding the axon guidance cues controlling the topographic sorting of thalamocortical axons in the ventral telencephalon.

Links: OMIM - NETRIN 1 | Mouse Development


  1. Sagai T, Amano T, Maeno A, Ajima R & Shiroishi T. (2019). SHH signaling mediated by a prechordal and brain enhancer controls forebrain organization. Proc. Natl. Acad. Sci. U.S.A. , , . PMID: 31685615 DOI.
  2. Kinare V, Pal S & Tole S. (2019). LDB1 Is Required for the Early Development of the Dorsal Telencephalon and the Thalamus. eNeuro , 6, . PMID: 30873428 DOI.
  3. Konno D, Iwashita M, Satoh Y, Momiyama A, Abe T, Kiyonari H & Matsuzaki F. (2012). The mammalian DM domain transcription factor Dmrta2 is required for early embryonic development of the cerebral cortex. PLoS ONE , 7, e46577. PMID: 23056351 DOI.
  4. Judaš M, Sedmak G, Pletikos M & Jovanov-Milošević N. (2010). Populations of subplate and interstitial neurons in fetal and adult human telencephalon. J. Anat. , 217, 381-99. PMID: 20979586 DOI.
  5. Rudolph J, Zimmer G, Steinecke A, Barchmann S & Bolz J. (2010). Ephrins guide migrating cortical interneurons in the basal telencephalon. Cell Adh Migr , 4, 400-8. PMID: 20473036
  6. Roth M, Bonev B, Lindsay J, Lea R, Panagiotaki N, Houart C & Papalopulu N. (2010). FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation. Development , 137, 1553-62. PMID: 20356955 DOI.
  7. Nieuwenhuys R. (2012). The insular cortex: a review. Prog. Brain Res. , 195, 123-63. PMID: 22230626 DOI.
  8. Rose M. Die Inselrinde des Menschen und der Tiere. (1928) Journal fuer Psychologie und Neurologie, 37: 467–624
  9. Mesulam MM. and Mufson EJ. The insula of Reil in man and monkey. (1985) A. Peters, E.G. Jones (Eds.), Association and auditory cortices, Plenum, New York, pp. 179–226
  10. Gohlke JM, Armant O, Parham FM, Smith MV, Zimmer C, Castro DS, Nguyen L, Parker JS, Gradwohl G, Portier CJ & Guillemot F. (2008). Characterization of the proneural gene regulatory network during mouse telencephalon development. BMC Biol. , 6, 15. PMID: 18377642 DOI.
  11. 11.0 11.1 Powell AW, Sassa T, Wu Y, Tessier-Lavigne M & Polleux F. (2008). Topography of thalamic projections requires attractive and repulsive functions of Netrin-1 in the ventral telencephalon. PLoS Biol. , 6, e116. PMID: 18479186 DOI.
  12. Dufour A, Seibt J, Passante L, Depaepe V, Ciossek T, Frisén J, Kullander K, Flanagan JG, Polleux F & Vanderhaeghen P. (2003). Area specificity and topography of thalamocortical projections are controlled by ephrin/Eph genes. Neuron , 39, 453-65. PMID: 12895420


Nomura T, Hattori M & Osumi N. (2009). Reelin, radial fibers and cortical evolution: insights from comparative analysis of the mammalian and avian telencephalon. Dev. Growth Differ. , 51, 287-97. PMID: 19210541 DOI.

Hébert JM & Fishell G. (2008). The genetics of early telencephalon patterning: some assembly required. Nat. Rev. Neurosci. , 9, 678-85. PMID: 19143049 DOI.


Yu W, Wang Y, McDonnell K, Stephen D & Bai CB. (2009). Patterning of ventral telencephalon requires positive function of Gli transcription factors. Dev. Biol. , 334, 264-75. PMID: 19632216 DOI.

Gulacsi AA & Anderson SA. (2008). Beta-catenin-mediated Wnt signaling regulates neurogenesis in the ventral telencephalon. Nat. Neurosci. , 11, 1383-91. PMID: 18997789 DOI.

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Rash BG & Grove EA. (2007). Patterning the dorsal telencephalon: a role for sonic hedgehog?. J. Neurosci. , 27, 11595-603. PMID: 17959802 DOI.

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