Spatiotemporal distribution of dying neurons during early mouse development

Authors

  • S. M. Van Den Eijnde,

    1. MGC Department of Clinical Genetics, Erasmus University Medical School, PO Box 1738, 3000DR Rotterdam, the Netherlands
    2. Institute of Plastic Surgery, Erasmus University Medical School, PO Box 1738, 3000DR Rotterdam, the Netherlands
    3. Department of Anatomy, Erasmus University Medical School, PO Box 1738, 3000DR Rotterdam, the Netherlands
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  • J. Lips,

    1. Department of Anatomy, Erasmus University Medical School, PO Box 1738, 3000DR Rotterdam, the Netherlands
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  • L. Boshart,

    1. MGC Department of Clinical Genetics, Erasmus University Medical School, PO Box 1738, 3000DR Rotterdam, the Netherlands
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  • C. Vermeij-Keers,

    1. Department of Anatomy, Erasmus University Medical School, PO Box 1738, 3000DR Rotterdam, the Netherlands
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  • E. Marani,

    1. Department of Physiology, Leiden State University Medical School, PO Box 9602, 2300 RC Leiden, the Netherlands
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  • C. P. M. Reutelingsperger,

    1. Department of Biochemistry, Cardiovascular Research Institute Maastricht, University of Maastricht, Universiteitssingel 50, 6229ER Maastricht, the Netherlands
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  • C. I. De Zeeuw

    1. Department of Anatomy, Erasmus University Medical School, PO Box 1738, 3000DR Rotterdam, the Netherlands
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Stefan M. van den Eijnde, Institute of Plastic Surgery, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: vandeneijnde@ikg.fgg.eur.nl. Also Chris I. De Zeeuw, as above. E-mail: dezeeuw@anat.fgg.eur.nl

Abstract

Apoptosis is a critical cellular event during several stages of neuronal development. Recently, we have shown that biotinylated annexin V detects apoptosis in vivo in various cell lineages of a wide range of species by binding to phosphatidylserines that are exposed at the outer leaflet of the plasma membrane. In the present study, we tested the specificity by which annexin V binds apoptotic neurons, and subsequently investigated developmental cell death in the central and peripheral nervous system of early mouse embryos at both the cellular and histological level, and compared the phagocytic clearance of apoptotic neurons with that of apoptotic mesodermal cells. Our data indicate: (i) that biotinylated annexin V can be used as a sensitive marker that detects apoptotic neurons, including their extensions at an early stage during development; (ii) that apoptosis plays an important part during early morphogenesis of the central nervous system, and during early quantitative matching of brain-derived neurotrophic factor and neurotrophic factor 3 responsive postmitotic large clear neurons in the peripheral ganglia with their projection areas; and (iii) that apoptotic neurons are removed by a process that differs from classical phagocytosis of non-neuronal tissues.

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