Skip to main content
Springer Nature Link
Log in

The human brain at stages 21–23, with particular reference to the cerebral cortical plate and to the development of the cerebellum

  • Published:
Save article
View saved research
Anatomy and Embryology Aims and scope Submit manuscript

Summary

The development of the human brain during the eighth embryonic week was studied in serial sections of 22 embryos, and graphic reconstructions were prepared. The cortical plate appears in stage 21 in the area of the future insula and is an excellent feature for staging. The internal capsule contains neocortical fibres. Its three main outlets begin to be present in stage 22 and lead to epithalamus, to dorsal thalamus, and to mesencephalon. At this time a well developed lateral olfactory tract can be seen. The anterior commissure appears in stage 23. A clear developmental relationship between claustrum and olfactory area is described for the first time in human embryos. The optic tract reaches the ventral area of the lateral geniculate body. Scattered fibres of the lateral lemniscus reach at least as far as the caudal mesencephalon, in which superior and inferior colliculi can be distinguished at stage 23; two caudalBlindsäcke containing ventricular recesses form in stage 23. The cerebellum is still present as a plate, but its internal bulge is considerably enlarged. It possesses radially- and tangentially-arranged cells; the latter form the external germinal layer. The dentate nucleus, as well as the inferior and superior cerebellar peduncles and some of the cerebellar commissures, are present. Compared with the highly developed and probably already functional remainder of the hindbrain, the cerebellar plate shows far less differentiation. Two caudal migratory streams (marginal and submarginal) are present and represent the corpus pontobulbare. The decussation of the pyramids appears in stage 23.

This article concludes the study of the developing human brain during the embryonic period, from stage 8 to stage 23. The series was based on 340 serially-sectioned embryos and graphic reconstructions from 89 brains. No comparable investigation of the fetal brain is available.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

References

  • Altman J (1982) Morphological development of the rat cerebellum and some of its mechanisms. In: Palay SL, Chan-Palay V (eds) The cerebellum-new vistas. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Altman J, Bayer SA (1978) Prenatal development of the cerebellar system in the rat. II. Cytogenesis and histogenesis of the inferior olive, pontine gray, and the precerebellar reticular nuclei. J Comp Neurol 179:49–75

    Article  PubMed  CAS  Google Scholar 

  • Altman J, Bayer SA (1985a, b, c) Embryonic development of the rat cerebellum. I. Delineation of the cerebellar primordium and early cell movements. II. Translocation and regional distribution of the deep neurons. III. Regional differences in the time of origin, migration, and settling of Purkinje cells. J Comp Neurol 231:1–26, 27–41, 42–65.

    Article  PubMed  CAS  Google Scholar 

  • Altman J, Bayer SA (1986) The development of the rat hypothalamus. Adv Anat Embryol Cell Biol 100:1–178

    PubMed  CAS  Google Scholar 

  • Ariëns Kappers CU (1982) The paraphysis cerebri. In: Crosby EC, Schnitzlein HN (eds) Comparative correlative neuroanatomy of the vertebrate telencephalon. Macmillan, New York, pp 249–265

    Google Scholar 

  • Bartelmez GW, Dekaban AS (1962) The early development of the human brain. Contrib Embryol Carnegie Instn 37:13–32

    Google Scholar 

  • Bayer SA (1980a) Development of the hippocampal region in the rat. I. Neurogenesis examined with3H-thymidine autoradiography. II. Morphogenesis during embryonic and early postnatal life. J Comp Neurol 190:87–114, 115–134

    Article  PubMed  CAS  Google Scholar 

  • Bayer SA (1980b) Quantitative3H-thymidine radiographic analyses of neurogenesis in the rat amygdala. J Comp Neurol 194:845–875

    Article  PubMed  CAS  Google Scholar 

  • Bayer SA (1984) Neurogenesis in the rat neostriatum. J Dev Neurosci 2:163–175

    Article  Google Scholar 

  • Bayer SA, Altman JA (1987) Directions in neurogenetic gradients and patterns of anatomical connections in the telencephalon. Prog Neurobiol 29:57–106

    Article  PubMed  CAS  Google Scholar 

  • Bayer SA, Altman J (1990) Development of layer I and the subplate in the rat neocortex. Exp Neurol 107:48–62

    Article  PubMed  CAS  Google Scholar 

  • Bourrat F, Sotelo C (1986) Neuronal migration and dendritic maturation of the medial cerebellar nucleus in rat embryos: an HRP in vitro study using cerebellar slabs. Brain Res 378:69–85

    Article  PubMed  CAS  Google Scholar 

  • Brown JW (1965) Some aspects of the early development of the hippocampal formation in certain insectivorous bats. In: Hassler R, Stephan H (eds) Evolution of the forebrain. Thieme, Stuttgart

    Google Scholar 

  • Brun A (1965) The subpial granular layer of the foetal cerebral cortex in man. Acta Pathol Microbiol Immunol Scand [B] 179:1–33

    Google Scholar 

  • Brundin P, Strecker RE, Clarke DJ, Widner H, Nilsson OG, Astedt B, Lindvall O, Björklund A (1988) Can human fetal dopamine neuron grafts provide a therapy for Parkinson’s disease? Gash DM, Sladek JR (eds) Prog Brain Res, vol 78, Chapter 57: Transplantation into the Mammalian CNS

  • Carpenter MB, Batton RR (1982) Connections of the fastigial nucleus in the cat and monkey. Exp Brain Res [Suppl 6]:250–291

    Google Scholar 

  • Chun JJM, Nakamura MJ, Shatz CJ (1987) Transient cells of the developing mammalian telencephalon are peptide-immunreactive neurons. Nature 325:617–620

    Article  PubMed  CAS  Google Scholar 

  • Cooper ERA (1945) The development of the human lateral geniculate body. Brain 68:222–239

    Google Scholar 

  • Cooper ERA (1946) Accessory optic tracts in the human fetus. Brain 69:45–49

    Google Scholar 

  • Cooper ERA (1947) The trochlear nerve in the human embryo and fetus. Br J Ophthalmol 31:257–275

    PubMed  CAS  Google Scholar 

  • Cooper ERA (1948) The development of the human auditory pathway from the cochlear ganglion to the medial geniculate body. Acta Anat 5:99–122

    PubMed  CAS  Google Scholar 

  • Crosby CE, Humphrey T, Lauer EW (1962) Correlative anatomy of the nervous system. Macmillan, New York

    Google Scholar 

  • Eckenhoff MF, Rakic P (1984) Radial organization of the hippocampal dentate gyrus: A golgi, ultrastructural, and immunocytochemical analysis in the developing rhesus monkey. J Comp Neurol 223:1–21

    Article  PubMed  CAS  Google Scholar 

  • Edwards MA, Caviness VS, Schneidet GD (1986) Development of cell and fiber lamination in the mouse superior colliculus. J Comp Neurol 248:395–409

    Article  PubMed  CAS  Google Scholar 

  • Essick CR (1912) The development of the nuclei pontis and the nucleus arcuatus in man. Am J Anat 13:25–54

    Article  Google Scholar 

  • Fentress IC, Stanfield BB, Cowan WM (1981) Observations on the development of the striatum in mice and rats. Anat Embryol 163:275–298

    Article  PubMed  CAS  Google Scholar 

  • Filimonoff IN (1966) The claustrum, its origin and development. J Hirnforsch 8:503–528

    PubMed  CAS  Google Scholar 

  • Fredericks CA, Giolli RA, Blanks RHI, Sadun AA (1988) The human accessory optic system. Brain Res 454:116–122

    Article  PubMed  CAS  Google Scholar 

  • Gilbert MS (1935) The early development of the human diencephalon. J Comp Neurol 62:81–115

    Article  Google Scholar 

  • Goffinet AM (1983) The embryonic development of the cerebellum in normal and reeler mutant mice. Anat Embryol 168:73–86

    Article  PubMed  CAS  Google Scholar 

  • Gould BB, Rakic P (1981) The total number, time of origin and kinetics of proliferation of neurons comprising the deep cerebellar nuclei in the rhesus monkey. Exp Brain Res 44:195–206

    Article  PubMed  CAS  Google Scholar 

  • Hallonet ME, Teillet MA, Le Douarin NM (1990) A new approach to the development of the cerebellum provided by the quailchick marker system. Development 108:19–31

    PubMed  CAS  Google Scholar 

  • Hewitt W (1958) The development of the human caudate and amgdaloid nuclei. J Anat 92:377–382

    PubMed  CAS  Google Scholar 

  • Hinds JW, Ruffett TL (1971) Cell proliferation in the neural tube: an electron microscopic and Golgi analysis in the mouse cerebral vesicle. Z Zellforsch 115:226–264

    Article  PubMed  CAS  Google Scholar 

  • His W (1904) Die Entwicklung des menschlichen Gehirns während der ersten Monate. Untersuchungsergebnisse. Hirzel, Leipzig

    Google Scholar 

  • Hochstetter F (1929) Beiträge zur Entwicklungsgeschichte des menschlichen Gehirns. II. Teil, 3. Lieferung. Die Entwicklung des Mittel- und Rautenhirns. Deuticke, Vienna

    Google Scholar 

  • Humphrey T (1960) The development of the pyramidal tracts in human fetuses, correlated with cortical differentiation. In: Tower DB, Schade JP (eds) Structure and function of the cerebral cortex. Elsevier, Amsterdam, pp 93–103

    Google Scholar 

  • Hynes RO, Patel R, Miller RH (1986) Migration of neuroblasts along pre-existing axonal tracts during prenatal cerebellar development. J Neurosci 6:867–876

    PubMed  CAS  Google Scholar 

  • Jones EG (1986) The Thalamus. Plenum, New York

    Google Scholar 

  • Kahle W (1969) Die Entwicklung der menschlichen Großhirnhemisphäre. Springer, Berlin: Schriftenreihe Neurologie 1:1–116

    Google Scholar 

  • Keyser A (1972) The development of the diencephalon of the chinese hamster. Acta Anat [Suppl 59]:1–178

    Google Scholar 

  • Kostović I, Krmpotić J (1976) Early prenatal ontogenesis of the neuronal connections in the interhemispheric cortex of the human gyrus cinguli. Verh Anat Ges 70:305–316

    PubMed  Google Scholar 

  • Kostović I, Rakic P (1980) Cytology and time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol 9:219–242

    Article  PubMed  Google Scholar 

  • Kuhlenbeck H (1977) Derivatives of the prosencephalon: Diencephalon and telencephalon. In: The central nervous system of vertebrates, vol 5, Part I. Karger, Basel, pp 461–888

    Google Scholar 

  • Laissue J (1963) Die histogenetische Gliederung der Rindenanlage des Endhirns. Acta Anat 53:158–185

    Article  PubMed  CAS  Google Scholar 

  • Lammers GJ (1976) On the development of the strio-amygdaloid complex in the chinese hamster,Cricetulus griseus. Thesis, Brakkenstein, Nijmegen

    Google Scholar 

  • Larsell O (1947) The development of the cerebellum in man in relation to its comparative anatomy. J Comp Neurol 87:85–129

    Article  PubMed  CAS  Google Scholar 

  • Levitt P, Rakic P (1982) The time of genesis, embryonic origin and differentiation of the brain stem monoamine neurons in the rhesus monkey. Dev Brain Res 4:35–57

    Article  Google Scholar 

  • Marchand R (1987) Histogenesis of the subthalamic nucleus. Neuroscience 21:183–195

    Article  PubMed  CAS  Google Scholar 

  • Marchand R, Poirier LJ (1983) Isthmic origin of neurons of the rat substantia nigra. Neuroscience 9:373–381

    Article  PubMed  CAS  Google Scholar 

  • Marin-Padilla M (1984) Neurons of Layer I. A developmental analysis. In: Peters A, Jones EG (eds) Cerebral cortex, vol 1. Chapter 14:447–478

    Google Scholar 

  • McConnell SK, Ghosh A, Shaty CJ (1989) Subplate neurons pioneer the first axon pathway from the cerebral cortex. Science 245:978–982

    PubMed  CAS  Google Scholar 

  • Molliver ME, Kostović I, van der Loos H (1973) The development of synapses in cerebral cortex of the human fetus. Brain Res 50:403–407

    Article  PubMed  CAS  Google Scholar 

  • Morris RJ, Beech JN, Heizmann CW (1988) Two distinct phases and mechanisms of axonal growth shown by primary vestibular fibres in the brain, demonstrated by parvalubin immunohistochemistry. Neuroscience 27:571–596

    Article  PubMed  CAS  Google Scholar 

  • Müller F, O’Rahilly R (1980) The human chondrocranium at the end of the embryonic period proper, with particular reference to the nervous system. Am J Anat 159:33–58

    Article  PubMed  Google Scholar 

  • Müller F, O’Rahilly R (1988) The first appearance of the future cerebral hemispheres in the human embryo at stage 14. Anat Embryol 177:495–511

    Article  PubMed  Google Scholar 

  • Müller F, O’Rahilly R (1990) The human brain at stages 18–20, including the choroid plexuses and the amygdaloid and septal nuclei. Anat Embryol 182:285–306

    Article  PubMed  Google Scholar 

  • Mrzljak L, Uylings HBM, Kostović I, van Eden CG (1988) Prenatal development of neurons in the human prefrontal cortex: I. A qualitative study. J Comp Neurol 271:355–386

    Article  PubMed  CAS  Google Scholar 

  • Nowakowski RS, Rakic P (1979) The mode of migration of neurons to the hippocampus: a Golgi and electron microscopic analysis in foetal rhesus monkey. J Neurocytol 8:697–718

    Article  PubMed  CAS  Google Scholar 

  • Ogren MP, Rakic P (1981) The prenatal development of the pulvinar in the monkey:3H-thymidine autoradiographic and morphometric analyses. Anat Embryol 162:1–20

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • O’Rahilly R, Müller F (1987) Development stages in human embryos including a revision of Streeter’s “Horizons” and a Survey of the Carnegie Collection. Carnegie Instn of Washington, Washington, DC, Publication, no 637

  • O’Rahilly R, Müller F, Bossy J (1982) Atlas des stades du développement du système nerveux chez l’embryon humain intact. Arch Anat Histol Embryol 65:57–76

    Google Scholar 

  • O’Rahilly R, Müller F, Hutchins GM, Moore GW (1984) Computer ranking of the sequence of appearance of 100 features of the brain and related structures in staged human embryos during the first 5 weeks of development. Am J Anat 171:243–257

    Article  PubMed  CAS  Google Scholar 

  • O’Rahilly R, Müller F, Bossy J (1986) Atlas des stades du développement des formes extérieures de l’encéphale chez l’embryon humain. Arch Anat Histol Embryol 69:3–39

    PubMed  CAS  Google Scholar 

  • O’Rahilly R, Müller F, Hutchins GM, Moore GW (1987) Computer ranking of the sequence of appearance of 73 features of the brain and related structures in staged human embryos during the sixth week of development. Am J Anat 180:69–86

    Article  PubMed  CAS  Google Scholar 

  • O’Rahilly R, Müller F, Hutchins GM, Moore GW (1988) Computer ranking of the sequence of appearance of 40 features of the brain and related structures in staged human embryos during the seventh week of development. Am J Anat 182:295–317

    Article  PubMed  CAS  Google Scholar 

  • O’Rahilly R, Müller F, Bossy J (1990) Atlas des stades du développement de l’encéphale chez l’embryon humain étudié par des réconstructions graphiques du plan médian. Arch Anat Histol Embryol. In press

  • Orts Llorca F (1977) Morfogenesis de los tuberculos mamilares (“Corpora mamillaria”) Arch Neurobiol 40:139–164

    CAS  Google Scholar 

  • Pearson AA (1939) The hypoglossal nerve in human embryos. J Comp Neurol 71:21–39

    Article  Google Scholar 

  • Pearson AA (1941a) The development of the nervus terminalis in man. J Comp Neurol 75:39–66

    Article  Google Scholar 

  • Pearson AA (1941b) The development of the olfactory nerve in man. J Comp Neurol 75:199–217

    Article  Google Scholar 

  • Pearson AA (1943) The trochlear nerve in human fetuses. J Comp Neurol 78:29–43

    Article  Google Scholar 

  • Pearson AA (1946) The development of the motor nuclei of the facial nerve in man. J Comp Neurol 85:461–476

    Article  PubMed  CAS  Google Scholar 

  • Pearson AA (1949a) The development and connections of the mesencephalic root of the trigeminal nerve in man. J Comp Neurol 90:1–46

    Article  PubMed  CAS  Google Scholar 

  • Pearson AA (1949b) Further observations on the mesencephalic root of the trigeminal nerve. J Comp Neurol 91:142–194

    Article  Google Scholar 

  • Rakic P (1974) Embryonic development of the pulvinar-LP complex in man. In: Cooper IS, Rakic P (eds) The Pulvinar-LP complex. Thomas, Springfield, Illinois, pp 3–35

    Google Scholar 

  • Rakic P (1977) Genesis of the dorsal lateral geniculate nucleus in the rhesus monkey: site and time of origin, kinetics of proliferation, routes of migration and pattern of distribution of neurons. J Comp Neurol 176:23–52

    Article  PubMed  CAS  Google Scholar 

  • Rakic P, Nowakowski RS (1981) The time of origin of neurons in the hippocampal region of the rhesus monkey. J Comp Neurol 196:99–128

    Article  PubMed  CAS  Google Scholar 

  • Rakic P, Sidman RL (1969) Telencephalic origin of pulvinar neurons in the fetal human brain. Z Anat Entwicklungsgesch 129:53–82

    Article  PubMed  CAS  Google Scholar 

  • Ricardo JA, Koh ET (1978) Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Brain Research 153:1–26

    Article  PubMed  CAS  Google Scholar 

  • Rickmann M, Wolff JR (1985) Prenatal gliogenesis in the neopallium of the rat. Adv Anat Embryol Cell Biol 93:1–104

    PubMed  CAS  Google Scholar 

  • Rickmann M, Chronwall BM, Wolff JR (1979) On the development of non-pyramidal neurons and axons outside the cortical plate: the early marginal zone as a pallial anlage. Anat Embryol 151:285–307

    Article  Google Scholar 

  • Rickmann M, Amari DG, Cowan WM (1987) Organization of radial glial cells during the development of the rat dentate gyrus. J Comp Neurol 264:449–479

    Article  PubMed  CAS  Google Scholar 

  • Sabin FR (1901) An atlas of the medulla and midbrain. Friedenwald, Baltimore

    Google Scholar 

  • Shaner RF (1932) The development of the nuclei and tracts of the midbrain. J Comp Neurol 55:493–504

    Article  Google Scholar 

  • Shatz CJ, Chun JJ, Luskin MB (1988) The role of the subplate in the development of the mammalian telencephalon. In: Peters A, Jones EG (eds) Cerebral cortex, vol 7. Plenum, New York, pp 35–58

    Google Scholar 

  • Sherk H (1986) The claustrum and the cerebral cortex. In: Jones EG, Peters A (eds) Cerebral cortex, vol 5. Plenum, New York, pp 467–495

    Google Scholar 

  • Shuangshoti S, Netsky MG (1966) Histogenesis of choroid plexus in man. Am J Anat 118:283–315

    Article  PubMed  CAS  Google Scholar 

  • Sidman RL, Rakic P (1982) Development of the human central nervous system. In: Haymaker W, Adams RD (eds) Histology and histopathology of the nervous system, vol 1. Thomas, Springfield

    Google Scholar 

  • Smart IHM (1976) A pilot study of cell production by the ganglionic eminences of the developing mouse brain. J Anat 121:71–84

    PubMed  CAS  Google Scholar 

  • Smart IHM, McSherry GM (1982) Growth patterns in the lateral wall of the mouse telencephalon. II. Histological changes during and subsequent to the period of isocortical neuron production. J Anat 134:415–442

    PubMed  CAS  Google Scholar 

  • Spector R, Johanson CE (1989) The mammalian choroid plexus. Sci Am 261:68–74

    Article  PubMed  CAS  Google Scholar 

  • Stensaas LJ (1967) The development of hippocampal and dorsolateral pallial regions of the cerebral hemisphere in fetal rabbits. I. Fifteen millimeter stage, spongioblast morphology. J Comp Neurol 129:59–69

    Article  Google Scholar 

  • Takeuchi Y, Matsushima S, Matsushima R, Hopkins DA (1983) Direct amygdaloid projections to the dorsal motor nucleus of the vagus nerve: a light and electron microscopic study in the rat. Brain Res 280:143–147

    Article  PubMed  CAS  Google Scholar 

  • Tello JF (1934) Les différenciations neurofibrillaires dans le prosencéphale de la souris de 4 a 15 millimètres. Trav Lab Rech Biol Univ Madrid 29:339–395

    Google Scholar 

  • Tello JF (1938) Histogenèse du cervelet et ses voies chez la souris blanche. Trav Lab Rech Biol Univ Madrid 32:1–74

    Google Scholar 

  • Turkewitsch N (1935) Die Entwicklung des Aquaeductus cerebri des Menschen. Morphol Jahrb 76:421–447

    Google Scholar 

  • van der Kooy D, Koda LY, McGinty JF, Gerfen ChR, Bloom FE (1984) The organization of projections from the cortex, amygdala, and hypothalamus to the nucleus of the solitary tract in rat. J Comp Neurol 224:1–24

    Article  PubMed  Google Scholar 

  • Verbitskaya LB (1969) Some aspects of the ontophylogenesis of the cerebellum. In: Llinas R (ed) Neurobiology of cerebellar evolution and development. Proc Inst Biomed Res Am Med Ass, Chicago

    Google Scholar 

  • de Vries JIP, Visser GHA, Prechtl HFR (1982) The emergence of fetal behaviour. I. Qualitative aspects. Early Hum Dev 7:301–322

    Article  PubMed  Google Scholar 

  • Wilson EE, Windle WF, Fitzgerald JE (1941) Development of the tractus solitarius. J Comp Neurol 74:287–307

    Article  Google Scholar 

  • Windle WF (1970) Development of neural elements in human embryos of four to seven weeks gestation. Exp Neurol [Suppl 5] 28:44–83

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Carnegie Laboratories of Embryology, California Primate Research Center, and Departments of Human Anatomy and Neurology, University of California, 95617, Davis, CA, USA

    F. Müller &  R. O’Rahilly

Authors
  1. F. Müller
    View author publications

    Search author on:PubMed Google Scholar

  2. R. O’Rahilly
    View author publications

    Search author on:PubMed Google Scholar

Additional information

Supported by research grant No. HD-16702, Institute of Child Health and Human Development, National Institutes of Health (USA)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Müller, F., O’Rahilly, R. The human brain at stages 21–23, with particular reference to the cerebral cortical plate and to the development of the cerebellum. Anat Embryol 182, 375–400 (1990). https://doi.org/10.1007/BF02433497

Download citation

  • Accepted:

  • Issue date:

  • DOI: https://doi.org/10.1007/BF02433497

Key words