Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Sign up for alerts
  • About us
    • About Development
    • About the Node
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contacts
    • Subscriptions
    • Feedback
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in
  • Log out

Search

  • Advanced search
Development
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Development

  • Log in
Advanced search

RSS  Twitter  Facebook  YouTube 

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Sign up for alerts
  • About us
    • About Development
    • About the Node
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contacts
    • Subscriptions
    • Feedback
JOURNAL ARTICLES
Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex
A.J. Blaschke, K. Staley, J. Chun
Development 1996 122: 1165-1174;
A.J. Blaschke
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
K. Staley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Chun
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & metrics
  • PDF
Loading

Summary

A key event in the development of the mammalian cerebral cortex is the generation of neuronal populations during embryonic life. Previous studies have revealed many details of cortical neuron development including cell birthdates, migration patterns and lineage relationships. Programmed cell death is a potentially important mechanism that could alter the numbers and types of developing cortical cells during these early embryonic phases. While programmed cell death has been documented in other parts of the embryonic central nervous system, its operation has not been previously reported in the embryonic cortex because of the lack of cell death markers and the difficulty in following the entire population of cortical cells. Here, we have investigated the spatial and temporal distribution of dying cells in the embryonic cortex using an in situ endlabelling technique called ‘ISEL+’ that identifies fragmented nuclear DNA in dying cells with increased sensitivity. The period encompassing murine cerebral cortical neurogenesis was examined, from embryonic days 10 through 18. Dying cells were rare at embryonic day 10, but by embryonic day 14, 70% of cortical cells were found to be dying. This number declined to 50% by embryonic day 18, and few dying cells were observed in the adult cerebral cortex. Surprisingly, while dying cells were observed throughout the cerebral cortical wall, the majority were found within zones of cell proliferation rather than in regions of postmitotic neurons. These observations suggest that multiple mechanisms may regulate programmed cell death in the developing cortex. Moreover, embryonic cell death could be an important factor enabling the selection of appropriate cortical cells before they complete their differentiation in postnatal life.

Reference

    1. Abrams J. M.,
    2. White K.,
    3. Fessler L. I.,
    4. Steller H.
    (1993) Programmed cell death during Drosophila embryogenesis. Development 117, 29–43
    OpenUrlAbstract/FREE Full Text
    1. Austin C. P.,
    2. Cepko C. L.
    (1990) Cellular migration patterns in the developing mouse cerebral cortex. Development 110, 713–732
    OpenUrlAbstract/FREE Full Text
    1. Barres B. A.,
    2. Hart I. K.,
    3. Coles H. S.,
    4. Burne J. F.,
    5. Voyvodic J. T.,
    6. Richardson W. D.,
    7. Raff M. C.
    (1992) Cell death and control of cell survival in the oligodendrocyte lineage. Cell 70, 31–46
    OpenUrlCrossRefPubMedWeb of Science
    1. Bayer S.,
    2. Altman J.
    (1990) Development of layer I and the subplate in the rat neocortex. Exp. Neurol 107, 48–62
    OpenUrlCrossRefPubMedWeb of Science
    1. Berry M.,
    2. Rogers A. W.
    (1965) The migration of neuroblasts in the developing cerebral cortex. J. Anat 99, 691–709
    OpenUrlPubMedWeb of Science
    1. Boulder Committee
    (1970) Embryonic vertebrate central nervous system: revised terminology. Anat. Rec 166, 257–261
    OpenUrlCrossRefPubMed
    1. Caelles C.,
    2. Helmberg A.,
    3. Karin M.
    (1994) p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature 370, 220–223
    OpenUrlCrossRefPubMed
    1. Caviness V. S. J.
    (1982) Neocortical histogenesis in normal and reeler mice: a developmental study based upon [3H]thymidine autoradiography. Dev. Brain Res 4, 293–302
    OpenUrlCrossRef
    1. Caviness V. S. J.,
    2. Takahashi T.,
    3. Nowakowski R. S.
    (1995) Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model. Trends Neurosci 18, 379–383
    OpenUrlCrossRefPubMedWeb of Science
    1. Chun J. J. M.,
    2. Schatz D. G.,
    3. Oettinger M. A.,
    4. Jaenisch R.,
    5. Baltimore D.
    (1991) The recombination activating gene-1 (RAG-1) transcript is present in the murine central nervous system. Cell 64, 189–200
    OpenUrlCrossRefPubMedWeb of Science
    1. Chun J. J. M.,
    2. Shatz C. J.
    (1989) Interstitial cells of the adult neocortical white matter are the remnant of the early generated subplate neuron population. J. Comp. Neurol 282, 555–569
    OpenUrlCrossRefPubMedWeb of Science
    1. Clarke P. G.,
    2. Rogers L. A.,
    3. Cowan W. M.
    (1976) The time of origin and the pattern of survival of neurons in the isthmo-optic nucleus of the chick. J. Comp. Neurol 167, 125–142
    OpenUrlCrossRefPubMedWeb of Science
    1. Cowan W. M.,
    2. Fawcett J. W.,
    3. O'Leary D. D. M.,
    4. Stanfield B. B.
    (1984) Regressive events in neurogenesis. Science 225, 1258–1265
    OpenUrlAbstract/FREE Full Text
    1. Crespo D.,
    2. O'Leary D. D. M.,
    3. Cowan W. M.
    (1985) Changes in the numbers of optic nerve fibers during late prenatal and postnatal development in the albino rat. Dev. Brain Res 19, 129–134
    OpenUrlCrossRef
    1. Cunningham T. J.,
    2. Mohler I. M.,
    3. Giordano D. L.
    (1982) Naturally occurring neuron death in the ganglion cell layer of the neonatal rat: morphology and evidence for regional correspondence with neuron death in superior colliculus. Dev. Brain Res 2, 203–215
    1. Das G. D.
    (1979) Gliogenesis and ependymogenesis during embryonic development of the rat. An autoradiographic study. J. Neur. Sci 43, 193–204
    1. Davis A. A.,
    2. Temple S.
    (1994) A self-renewing multipotential stem cell in embryonic rat cerebral cortex. Nature 372, 263–266
    OpenUrlCrossRefPubMed
    1. Derer P.,
    2. Derer M.
    (1990) Cajal-Retzius cell ontogenesis and death in mouse brain visualized with horseradish peroxidase and electron mircroscopy. Neuroscience 36, 839–856
    OpenUrlCrossRefPubMedWeb of Science
    1. Egerton M.,
    2. Scollay R.,
    3. Shortman K.
    (1990) Kinetics of mature T-cell development in the thymus. Proc. Natl Acad. Sci. USA 87, 2579–2582
    OpenUrlAbstract/FREE Full Text
    1. Ferrer I.,
    2. Soriano E.,
    3. Del Rio J. A.,
    4. Alcantara S.,
    5. Auladell C.
    (1992) Cell Death and Removal in the Cerebral Cortex During Development. Prog. Neurobiol 39, 1–43
    OpenUrlCrossRefPubMedWeb of Science
    1. Finlay B. L.,
    2. Slattery M.
    (1983) Local differences in the amount of early cell death in neocortex predict adult local specializations. Science 219, 1349–1351
    OpenUrlAbstract/FREE Full Text
    1. Flanagan A. E.
    (1969) Differentiation and degeneration in the motor horn of the foetal mouse. J. Morph 129, 281–305
    OpenUrlCrossRefPubMedWeb of Science
    1. Gavrieli Y.,
    2. Sherman Y.,
    3. Ben-Sasson S. A.
    (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol 119, 493–501
    OpenUrlAbstract/FREE Full Text
    1. Hamburger V.
    (1975) Cell death in the development of the lateral motor column of the chick embryo. J. Comp. Neurol 160, 535–546
    OpenUrlCrossRefPubMedWeb of Science
    1. Hamburger V.,
    2. Levi-Montalcini R.
    (1949) Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J. Exp. Zool 111, 457–502
    OpenUrlCrossRefPubMedWeb of Science
    1. Heumann D.,
    2. Leuba G.
    (1983) Neuronal death in the development and aging of the cerebral cortex of the mouse. Neuropath. Appl. Neurobiol 9, 297–311
    OpenUrlPubMedWeb of Science
    1. Hicks S. P.,
    2. D'Amato C. J.
    (1968) Cell migrations to the isocortex in the rat. Anat. Rec 160, 619–634
    OpenUrlCrossRefPubMed
    1. Homma S.,
    2. Yaginuma H.,
    3. Oppenheim R. W.
    (1994) Programmed cell death during the earliest stages of spinal cord development in the chick embryo: a possible means of early phenotypic selection. J. Comp. Neurol 343, 377–395
    OpenUrl
    1. Horsburgh G. M.,
    2. Sefton A. J.
    (1987) Cellular degeneration and synaptogenesis in the developing retina of the rat. J. Comp. Neurol 263, 553–566
    OpenUrlCrossRefPubMedWeb of Science
    1. Kostovic I.,
    2. Rakic P.
    (1990) Developmental history of the transient subplate zone in the visual and somatosensory cortex of the macaque monkey and human brain. J. Comp. Neurol 297, 441–470
    OpenUrlCrossRefPubMedWeb of Science
    1. Lam K.,
    2. Sefton A. J.,
    3. Bennett M. R.
    (1982) Loss of axons from the optic nerve of the rat during early postnatal development. Brain Res 255, 487–491
    OpenUrlCrossRefPubMed
    1. Landmesser L.,
    2. Pilar G.
    (1974) Synaptic transmission and cell death during normal ganglionic development. J. Physiol 241, 737–749
    OpenUrl
    1. Linden R.,
    2. Pinto L. H.
    (1985) Developmental genetics of the retina: evidence that the pearl mutation in the mouse affects the time course of natural cell death in the ganglion cell layer. Exp. Brain Res 60, 79–86
    OpenUrlPubMedWeb of Science
    1. Luskin M. B.,
    2. Pearlman A. L.,
    3. Sanes J. R.
    (1988) Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a recombinant retrovirus. Neuron 1, 635–47
    OpenUrlCrossRefPubMedWeb of Science
    1. Matsuyama M.,
    2. Wiadrowski M. N.,
    3. Metcalf D.
    (1966) Autoradiographic analysis of lymphopoiesis and lymphocyte migration in mice bearing multiple thymus grafts. J. Exp. Med 123, 559–576
    OpenUrlAbstract
    1. Miller N.,
    2. Oberdorfer M.
    (1981) Neuronal and neuroglial responses following retinal lesions in the neonatal rats. J. Comp. Neurol 202, 493–504
    OpenUrlCrossRefPubMedWeb of Science
    1. Mission J. P.,
    2. Takahashi T.,
    3. Caviness V. S. J.
    (1991) Ontogeny of radial and other astroglial cells in murine cerebral cortex. Glia 4, 138–148
    OpenUrlCrossRefPubMedWeb of Science
    1. Oppenheim R. W.
    (1985) Naturally occurring cell death during neural development. Trends Neurosci 8, 487–493
    OpenUrlCrossRefWeb of Science
    1. Oppenheim R. W.
    (1991) Cell death during development of the nervous system. Ann. Rev. Neurosci 14, 453–501
    OpenUrlCrossRefPubMedWeb of Science
    1. Parnavelas J. G.,
    2. Barfield J. A.,
    3. Franke E.,
    4. Luskin M. B.
    (1991) Separate progenitor cells give rise to pyramidal and nonpyramidal neurons in the rat telencephalon. Cereb. Cort 1, 463–468
    OpenUrlAbstract/FREE Full Text
    1. Perry V. H.,
    2. Henderson Z.,
    3. Linden R.
    (1983) Postnatal changes in retinal ganglion cell and optic axon populations in the pigmented rat. J. Comp. Neurol 219, 356–368
    OpenUrlCrossRefPubMedWeb of Science
    1. Potts R. A.,
    2. Dreher B.,
    3. Bennett M. R.
    (1982) The loss of ganglion cells in the developing retina of the rat. Brain Res 255, 481–486
    OpenUrlPubMed
    1. Price D. J.,
    2. Blakemore C.
    (1985) Regressive events in the postnatal development of association projections in the visual cortex. Nature 316, 721–724
    OpenUrlCrossRefPubMed
    1. Price J.,
    2. Thurlow L.
    (1988) Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer. Development 104, 473–482
    OpenUrlAbstract/FREE Full Text
    1. Raff M. C.,
    2. Barres B. A.,
    3. Burne J. F.,
    4. Coles H. S.,
    5. Ishizaki Y.,
    6. Jacobson M. D.
    (1993) Programmed cell death and the control of cell survival: lessons from the nervous system. Science 262, 695–700
    OpenUrlAbstract/FREE Full Text
    1. Rakic P.
    (1976) Prenatal genesis of connections subserving ocular dominance in the rhesus monkey. Nature 261, 467–471
    OpenUrlCrossRefPubMed
    1. Rakic P.
    (1977) Prenatal development of the visual system in rhesus monkey. Phil. Trans. R. Soc. Lond 278, 245–260
    OpenUrlPubMedWeb of Science
    1. Saunders J. W.
    (1966) Death in embryonic systems. Science 154, 604–612
    OpenUrlAbstract/FREE Full Text
    1. Shatz C. J.,
    2. Rakic P.
    (1981) The genesis of efferent connections from the visual cortex of the fetal rhesus monkey. J. Comp. Neurol 196, 287–307
    OpenUrlCrossRefPubMedWeb of Science
    1. Shortman K.,
    2. Egerton M.,
    3. Spangrude G. J.,
    4. Scollay R.
    (1990) The generation and fate of thymocytes. Sem. Immunol 2, 3–12
    OpenUrlPubMed
    1. Surh C. D.,
    2. Sprent J.
    (1994) T-cell apoptosis detected in situduring positive and negative selection in the thymus. Nature 372, 100–103
    OpenUrlCrossRefPubMed
    1. Takahashi T.,
    2. Nowakowski R. S.,
    3. Caviness V. S.
    (1993) Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse. J. Neurosci 13, 820–833
    OpenUrlAbstract
    1. Takahashi T.,
    2. Nowakowski R. S.,
    3. Caviness V. S.
    (1995) The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J. Neurosci 15, 6046–6057
    OpenUrlAbstract
    1. Walsh C.,
    2. Cepko C. L.
    (1988) Clonally related cortical cells show several migration patterns. Science 241, 1342–1345
    OpenUrlAbstract/FREE Full Text
    1. White K.,
    2. Grether M. E.,
    3. Abrams J. M.,
    4. Young L.,
    5. Farrell K.,
    6. Steller H.
    (1994) Genetic control of programmed cell death in Drosophila. Science 264, 677–683
    OpenUrlAbstract/FREE Full Text
    1. Wijsman J. H.,
    2. Jonker R. R.,
    3. Keijzer R.,
    4. van de Velde C. J.,
    5. Cornelisse C. J.,
    6. van Dierendonck J. H.
    (1993) A new method to detect apoptosis in paraffin sections: in situ end-labeling of fragmented DNA. J. Histochem. Cytochem 41, 7–12
    OpenUrlAbstract/FREE Full Text
    1. Williams G. T.,
    2. Smith C. A.
    (1993) Molecular regulation of apoptosis: genetic controls on cell death. Cell 74, 777–779
    OpenUrlCrossRefPubMedWeb of Science
    1. Williams R. W.,
    2. Herrup K.
    (1988) The control of neuron number. Ann. Rev. Neurosci 11, 423–453
    OpenUrlCrossRefPubMedWeb of Science
    1. Wood J. G.,
    2. Martin S.,
    3. Price D. J.
    (1992) Evidence that the earliest generated cells of the murine cerebral cortex form a transient population in the subplate and marginal zone. Brain Res 66, 137–140
    1. Wood K. A.,
    2. Dipasquale B.,
    3. Youle R. J.
    (1993) In situ labeling of granule cells for apoptosis-associated DNA fragmentation reveals different mechanisms of cell loss in developing cerebellum. Neuron 11, 621–632
    OpenUrlCrossRefPubMedWeb of Science
    1. Woodhams P. L.,
    2. Basco E.,
    3. Hajos F.,
    4. Csillag A.,
    5. Balazs R.
    (1981) Radial glia in the developing mouse cerebral cortex and hippocampus. Anat. Embryol 163, 331–343
    OpenUrlCrossRefPubMed
    1. Wyllie A. H.
    (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284, 555–556
    OpenUrlCrossRefPubMed
    1. Wyllie A. H.,
    2. Morris R. G.,
    3. Smith A. L.,
    4. Dunlop D.
    (1984) Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J. Pathol 142, 67–77
    OpenUrlCrossRefPubMedWeb of Science
    1. Young R. W.
    (1984) Cell death during differentiation of the retina in the mouse. J. Comp. Neurol 229, 362–373
    OpenUrlCrossRefPubMedWeb of Science
Previous ArticleNext Article
Back to top
Previous ArticleNext Article

This Issue

 Download PDF

Email

Thank you for your interest in spreading the word on Development.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex
(Your Name) has sent you a message from Development
(Your Name) thought you would like to see the Development web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
JOURNAL ARTICLES
Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex
A.J. Blaschke, K. Staley, J. Chun
Development 1996 122: 1165-1174;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
JOURNAL ARTICLES
Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex
A.J. Blaschke, K. Staley, J. Chun
Development 1996 122: 1165-1174;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
  • Info & metrics
  • PDF

Related articles

Cited by...

More in this TOC section

  • Morphogenetic cell movements in the middle region of the dermomyotome dorsomedial lip associated with patterning and growth of the primary epaxial myotome
  • Germline and developmental roles of the nuclear transport factor importin (α)3 in C. elegans
  • Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo
Show more JOURNAL ARTICLES

Similar articles

Other journals from The Company of Biologists

Journal of Cell Science

Journal of Experimental Biology

Disease Models & Mechanisms

Biology Open

Advertisement

Kathryn Virginia Anderson (1952-2020)

Developmental geneticist Kathryn Anderson passed away at home on 30 November 2020. Tamara Caspary, a former postdoc and friend, remembers Kathryn and her remarkable contribution to developmental biology.


Zooming into 2021

In a new Editorial, Editor-in-Chief James Briscoe and Executive Editor Katherine Brown reflect on the triumphs and tribulations of the last 12 months, and look towards a hopefully calmer and more predictable year.


Read & Publish participation extends worldwide

Over 60 institutions in 12 countries are now participating in our Read & Publish initiative. Here, James Briscoe explains what this means for his institution, The Francis Crick Institute. Find out more and view our full list of participating institutions.


Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.


Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Sign up to join our next session:

10 February
Time: 13:00 (GMT)
Chaired by: preLights

Articles

  • Accepted manuscripts
  • Issue in progress
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Special issues
  • Subject collections
  • Sign up for alerts

About us

  • About Development
  • About the Node
  • Editors and board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Journal Meetings
  • Workshops
  • The Company of Biologists

For authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • Biology Open transfer

Journal info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Sign up for alerts

Contact

  • Contact Development
  • Subscriptions
  • Advertising
  • Feedback

 Twitter   YouTube   LinkedIn

© 2021   The Company of Biologists Ltd   Registered Charity 277992