Genetic regulation of proliferation/differentiation characteristics of neural progenitor cells in the developing neocortex

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Brain size variation among different mammals is tightly associated with different levels of cerebral function. Mechanisms that regulate the number of neurons and hence the size of the brain must be at least partially embedded within the very early phase of neocortical development, that is, embedded in proliferation/differentiation characteristics of the neural progenitor cells (NPCs) of the neocortex. Here we review a sequence of critical events through which the neocortex is formed in the embryonic forebrain, with particular emphasis on cell cycle kinetics of the NPCs that produce non-GABAergic projection neurons, the majority of neurons in the neocortex. In general, the critical parameters that determine the total number of cells produced by a given progenitor population through a sequence of cell cycles are (1) the number of cell cycles that constitute the production period and (2) the probability of cell cycle exit (Q fraction or Q) of progenitor cells for each of the cell cycles. We will also review molecular mechanisms that modulate the critical parameters above, with a special reference to the cell cycle regulatory protein p27Kip1, inhibitor of G1 phase progression of the cell cycle. Finally the neocortical dysgenesis caused by genetic modification in mice where p27Kip1 is either deleted or overexpressed is presented as examples of neuron number changes and resultant neocortical dysgenesis by Q fraction alteration.

Original languageEnglish
Pages (from-to)553-557
Number of pages5
JournalBrain and Development
Volume31
Issue number7
DOIs
Publication statusPublished - 2009 Aug

Fingerprint

Neocortex
Cell Cycle
Stem Cells
Neurons
Cell Cycle Proteins
Brain
G1 Phase
Prosencephalon
Mammals
Cell Count
Population

Keywords

  • CDKI
  • Cell cycle kinetics
  • Development
  • Neocortex

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Pediatrics, Perinatology, and Child Health

Cite this

@article{2097cf47439e46168293306ce8bb50cd,
title = "Genetic regulation of proliferation/differentiation characteristics of neural progenitor cells in the developing neocortex",
abstract = "Brain size variation among different mammals is tightly associated with different levels of cerebral function. Mechanisms that regulate the number of neurons and hence the size of the brain must be at least partially embedded within the very early phase of neocortical development, that is, embedded in proliferation/differentiation characteristics of the neural progenitor cells (NPCs) of the neocortex. Here we review a sequence of critical events through which the neocortex is formed in the embryonic forebrain, with particular emphasis on cell cycle kinetics of the NPCs that produce non-GABAergic projection neurons, the majority of neurons in the neocortex. In general, the critical parameters that determine the total number of cells produced by a given progenitor population through a sequence of cell cycles are (1) the number of cell cycles that constitute the production period and (2) the probability of cell cycle exit (Q fraction or Q) of progenitor cells for each of the cell cycles. We will also review molecular mechanisms that modulate the critical parameters above, with a special reference to the cell cycle regulatory protein p27Kip1, inhibitor of G1 phase progression of the cell cycle. Finally the neocortical dysgenesis caused by genetic modification in mice where p27Kip1 is either deleted or overexpressed is presented as examples of neuron number changes and resultant neocortical dysgenesis by Q fraction alteration.",
keywords = "CDKI, Cell cycle kinetics, Development, Neocortex",
author = "Takayuki Mitsuhashi and Takao Takahashi",
year = "2009",
month = "8",
doi = "10.1016/j.braindev.2009.05.002",
language = "English",
volume = "31",
pages = "553--557",
journal = "Brain and Development",
issn = "0387-7604",
publisher = "Elsevier",
number = "7",

}

TY - JOUR

T1 - Genetic regulation of proliferation/differentiation characteristics of neural progenitor cells in the developing neocortex

AU - Mitsuhashi, Takayuki

AU - Takahashi, Takao

PY - 2009/8

Y1 - 2009/8

N2 - Brain size variation among different mammals is tightly associated with different levels of cerebral function. Mechanisms that regulate the number of neurons and hence the size of the brain must be at least partially embedded within the very early phase of neocortical development, that is, embedded in proliferation/differentiation characteristics of the neural progenitor cells (NPCs) of the neocortex. Here we review a sequence of critical events through which the neocortex is formed in the embryonic forebrain, with particular emphasis on cell cycle kinetics of the NPCs that produce non-GABAergic projection neurons, the majority of neurons in the neocortex. In general, the critical parameters that determine the total number of cells produced by a given progenitor population through a sequence of cell cycles are (1) the number of cell cycles that constitute the production period and (2) the probability of cell cycle exit (Q fraction or Q) of progenitor cells for each of the cell cycles. We will also review molecular mechanisms that modulate the critical parameters above, with a special reference to the cell cycle regulatory protein p27Kip1, inhibitor of G1 phase progression of the cell cycle. Finally the neocortical dysgenesis caused by genetic modification in mice where p27Kip1 is either deleted or overexpressed is presented as examples of neuron number changes and resultant neocortical dysgenesis by Q fraction alteration.

AB - Brain size variation among different mammals is tightly associated with different levels of cerebral function. Mechanisms that regulate the number of neurons and hence the size of the brain must be at least partially embedded within the very early phase of neocortical development, that is, embedded in proliferation/differentiation characteristics of the neural progenitor cells (NPCs) of the neocortex. Here we review a sequence of critical events through which the neocortex is formed in the embryonic forebrain, with particular emphasis on cell cycle kinetics of the NPCs that produce non-GABAergic projection neurons, the majority of neurons in the neocortex. In general, the critical parameters that determine the total number of cells produced by a given progenitor population through a sequence of cell cycles are (1) the number of cell cycles that constitute the production period and (2) the probability of cell cycle exit (Q fraction or Q) of progenitor cells for each of the cell cycles. We will also review molecular mechanisms that modulate the critical parameters above, with a special reference to the cell cycle regulatory protein p27Kip1, inhibitor of G1 phase progression of the cell cycle. Finally the neocortical dysgenesis caused by genetic modification in mice where p27Kip1 is either deleted or overexpressed is presented as examples of neuron number changes and resultant neocortical dysgenesis by Q fraction alteration.

KW - CDKI

KW - Cell cycle kinetics

KW - Development

KW - Neocortex

UR - http://www.scopus.com/inward/record.url?scp=67649419546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649419546&partnerID=8YFLogxK

U2 - 10.1016/j.braindev.2009.05.002

DO - 10.1016/j.braindev.2009.05.002

M3 - Article

VL - 31

SP - 553

EP - 557

JO - Brain and Development

JF - Brain and Development

SN - 0387-7604

IS - 7

ER -