Overexpression of p27 Kip 1, probability of cell cycle exit, and laminar destination of neocortical neurons

Cereb Cortex. 2005 Sep;15(9):1343-55. doi: 10.1093/cercor/bhi017. Epub 2005 Jan 12.

Abstract

Neocortical projection neurons arise from a pseudostratified ventricular epithelium (PVE) from embryonic day 11 (E11) to E17 in mice. The sequence of neuron origin is systematically related to mechanisms that specify neuronal class properties including laminar fate destination. Thus, the neurons to be assembled into the deeper layers are the earliest generated, while those to be assembled into superficial layers are the later generated neurons. The sequence of neuron origin also correlates with the probability of cell cycle exit (Q) and the duration of G1-phase of the cell cycle (T(G1)) in the PVE. Both Q and T(G1) increase as neuronogenesis proceeds. We test the hypothesis that mechanisms regulating specification of neuronal laminar destination, Q and T(G1) are coordinately regulated. We find that overexpression of p27(Kip1) in the PVE from E12 to E14 increases Q but not T(G1) and that the increased Q is associated with a commensurate increase in the proportion of exiting cells that is directed to superficial layers. We conclude that mechanisms that govern specification of neocortical neuronal laminar destination are coordinately regulated with mechanisms that regulate Q and are independent of mechanisms regulatory to cell cycle duration. Moreover, they operate prior to postproliferative mechanisms necessary to neocortical laminar assembly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Animals
  • Antimetabolites / pharmacology
  • Apoptosis / physiology
  • Bromodeoxyuridine / pharmacology
  • Cell Count
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / biosynthesis*
  • Cell Cycle Proteins / genetics
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase Inhibitor p27
  • Female
  • Gene Expression
  • Idoxuridine / pharmacology
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Kinetics
  • Mice
  • Mice, Transgenic
  • Neocortex / anatomy & histology
  • Neocortex / cytology*
  • Neocortex / growth & development
  • Neurons / physiology*
  • S Phase / physiology
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • Antimetabolites
  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Bromodeoxyuridine
  • Idoxuridine