Lysophosphatidic acid (LPA) is a novel extracellular regulator of cortical neuroblast morphology

Dev Biol. 2000 Dec 1;228(1):6-18. doi: 10.1006/dbio.2000.9930.


During cerebral cortical neurogenesis, neuroblasts in the ventricular zone (VZ) undergo a shape change termed "interkinetic nuclear migration" whereby cells alternate between fusiform and rounded morphologies. We previously identified lp(A1), the first receptor gene for a signaling phospholipid called lysophosphatidic acid (LPA) and showed its enriched expression in the VZ. Here we report that LPA induces changes in neuroblast morphology from fusiform to round in primary culture, accompanied by nuclear movements, and formation of f-actin retraction fibers. These changes are mediated by the activation of the small GTPase, Rho. In explant cultures, where the cerebral cortical architecture remains intact, LPA not only induces cellular and nuclear rounding in the VZ, but also produces an accumulation of rounded nuclei at the ventricular surface. Consistent with a biological role for these responses, utilization of a sensitive and specific bioassay indicates that postmitotic neurons can produce extracellular LPA. These results implicate LPA as a novel factor in cortical neurogenesis and further implicate LPA as an extracellular signal from postmitotic neurons to proliferating neuroblasts.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Biological Transport
  • Cell Division
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Cell Size / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / pharmacology
  • Gene Expression Regulation, Developmental
  • Histocytochemistry
  • In Situ Hybridization
  • Lysophospholipids / analysis
  • Lysophospholipids / metabolism*
  • Lysophospholipids / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Scanning
  • Microscopy, Video
  • Models, Biological
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Organ Culture Techniques
  • Signal Transduction / drug effects
  • Stress Fibers / drug effects
  • rho GTP-Binding Proteins / metabolism


  • Actins
  • Culture Media, Conditioned
  • Lysophospholipids
  • rho GTP-Binding Proteins