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Cell cycle dependence of laminar determination in developing neocortex.

S K McConnell1, C E Kaznowski

  • 1Department of Biological Sciences, Stanford University, CA 94305.

Science (New York, N.Y.)
|October 11, 1991
PubMed
Summary

Neuronal development in the neocortex shows that progenitor cell cycle stage influences neuronal layer fate. Early cell cycle stages lead to superficial layer fates, while later stages commit to deep layers.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • The neocortex exhibits layered neuronal organization, with neurons generated sequentially during development.
  • A strong correlation exists between a neuron's birthdate and its final laminar position.
  • Understanding the mechanisms determining neuronal phenotypes in the developing cortex is crucial.

Purpose of the Study:

  • To investigate how neuronal phenotypes, specifically laminar fate, are determined in the developing neocortex.
  • To examine the role of progenitor cell cycle position in dictating neuronal layer identity.
  • To assess the influence of environmental cues versus intrinsic progenitor state on laminar fate.

Main Methods:

  • Labeling embryonic progenitor cells with [3H]thymidine at different developmental times.
  • Transplanting these labeled progenitor cells into older host brains.
  • Analyzing the laminar fate of transplanted neurons based on their progenitors' cell cycle stage at transplantation.

Main Results:

  • The laminar fate of transplanted neurons directly correlates with the cell cycle position of their progenitors at the time of transplantation.
  • Progenitors transplanted during the S-phase of the cell cycle generated neurons that migrated to superficial layers (e.g., layer 2/3).
  • Progenitors transplanted later in the cell cycle produced neurons committed to their normal, deep-layer fates, indicating intrinsic commitment.

Conclusions:

  • Environmental factors significantly influence neuronal laminar fate in the developing neocortex.
  • Embryonic progenitors exhibit cyclical changes in their responsiveness to environmental cues, dependent on their cell cycle stage.
  • The cell cycle position of progenitor cells is a critical determinant of neuronal layer specification, interacting with environmental signals.

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