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Programmed cell death in the developing human telencephalon.

S Rakic1, N Zecevic

  • 1Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030-3401, USA.

The European Journal of Neuroscience
|September 6, 2000
PubMed
Summary
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Programmed cell death (PCD) is crucial for human brain development. This study tracked apoptosis in the developing telencephalon, revealing distinct embryonic and fetal patterns.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Programmed cell death, specifically apoptosis, is fundamental to central nervous system development.
  • Understanding the temporal and spatial dynamics of apoptosis is key to comprehending human telencephalic formation.

Purpose of the Study:

  • To investigate the onset, extent, and distribution of programmed cell death (apoptosis) in the developing human telencephalon.
  • To differentiate between embryonic and fetal apoptosis patterns and their potential roles.

Main Methods:

  • Utilized the TUNEL (TdT-mediated dUTP-biotin nick-end labelling) in situ method to detect apoptotic nuclei.
  • Examined human embryos and fetuses across a gestational range of 4.5 to 27 weeks.
  • Employed double-labelling experiments to identify cell types undergoing apoptosis.

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Main Results:

  • Apoptotic nuclei were observed from 4.5 gestational weeks, initially sparse in the ventricular zone, and later distributed across cortical layers and subcortical regions.
  • Proliferative zones showed the highest numbers of apoptotic cells, while the subplate and layer I exhibited the highest apoptotic index.
  • Neuronal precursors were the primary apoptotic cells in the first trimester, with glial cells dying later; microglial involvement in PCD was also indicated.

Conclusions:

  • Two distinct phases of apoptosis were identified: embryonic apoptosis, linked to neuronal proliferation and migration, and fetal apoptosis, associated with differentiation and synaptogenesis.
  • Embryonic apoptosis appears unrelated to neuronal circuitry establishment, whereas fetal apoptosis may play a role in axonal-target connectivity development.