Periventricular notch activation and asymmetric Ngn2 and Tbr2 expression in pair-generated neocortical daughter cells

Mol Cell Neurosci. 2009 Feb;40(2):225-33. doi: 10.1016/j.mcn.2008.10.007. Epub 2008 Nov 7.

Abstract

To understand the cellular and molecular mechanisms regulating cytogenesis within the neocortical ventricular zone, we examined at high resolution the spatiotemporal expression patterns of Ngn2 and Tbr2. Individually DiI-labeled daughter cells were tracked from their birth in slice cultures and immunostained for Ngn2 and Tbr2. Both proteins were initially absent from daughter cells during the first 2 h. Ngn2 expression was then initiated asymmetrically in one of the daughter cells, with a bias towards the apical cell, followed by a similar pattern of expression for Tbr2, which we found to be a direct target of Ngn2. How this asymmetric Ngn2 expression is achieved is unclear, but gamma-secretase inhibition at the birth of daughter cells resulted in premature Ngn2 expression, suggesting that Notch signaling in nascent daughter cells suppresses a Ngn2-Tbr2 cascade. Many of the nascent cells exhibited pin-like morphology with a short ventricular process, suggesting periventricular presentation of Notch ligands to these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Benzodiazepinones / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Gene Expression Regulation, Developmental*
  • Mice
  • Neocortex* / cytology
  • Neocortex* / embryology
  • Neocortex* / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurogenesis / physiology*
  • Promoter Regions, Genetic
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Signal Transduction / physiology
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / physiology*
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*

Substances

  • 2-(((3,5-difluorophenyl)acetyl)amino)-N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)propanamide
  • Basic Helix-Loop-Helix Transcription Factors
  • Benzodiazepinones
  • Eomes protein, mouse
  • Nerve Tissue Proteins
  • Neurog2 protein, mouse
  • Receptors, Notch
  • T-Box Domain Proteins
  • Cyclin-Dependent Kinase Inhibitor p27