Cortical layer development and orientation is modulated by relative contributions of reelin-negative and -positive neurons in mouse chimeras

Cereb Cortex. 2010 Sep;20(9):2017-26. doi: 10.1093/cercor/bhp287. Epub 2010 Jan 6.

Abstract

Reelin is an important protein that is indispensable for cortical lamination. In the absence of Reelin, cortical layers fail to form due to inappropriate neuron migration and positioning. The inversion of cortical layers is attributed to failure of neurons to migrate past earlier-generated neurons although how Reelin-insufficiency causes this is unclear. The issue is complicated by recent studies showing that very little Reelin is required for cortical layering. To test how variation in the number of Reelin-producing cells is linked to cortical lamination, we have employed Reelin(+/+) <--> Reelin(-/-) chimeras in which the number of Reelin-expressing neurons is adjusted. We found that the Reeler phenotype was rescued in chimeras with a large contribution of Reelin(+/+) neurons; conversely in chimeras with a weak contribution by Reelin(+/+) neurons, the mutant phenotype remained. However, increasing the number of Reelin(+/+) neurons beyond an unknown threshold resulted in partial rescue, with the formation of a correctly layered secondary cortex lying on top of an inverted mutant cortex. Therefore, the development of cortical layers in the correct order requires a minimal level of Reelin protein to be present although paradoxically, this is insufficient to prevent the simultaneous formation of inverted cortical layers in the same hemisphere.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Body Patterning / genetics*
  • Cell Adhesion Molecules, Neuronal / biosynthesis*
  • Cell Adhesion Molecules, Neuronal / deficiency*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Movement / genetics
  • Cerebral Cortex / abnormalities*
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / metabolism
  • Extracellular Matrix Proteins / biosynthesis*
  • Extracellular Matrix Proteins / deficiency*
  • Extracellular Matrix Proteins / genetics
  • Female
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Nervous System Malformations / genetics
  • Nervous System Malformations / metabolism
  • Neurogenesis / genetics
  • Neurons / metabolism*
  • Neurons / pathology
  • Reelin Protein
  • Serine Endopeptidases / biosynthesis*
  • Serine Endopeptidases / deficiency*
  • Serine Endopeptidases / genetics
  • Transplantation Chimera / genetics*
  • Transplantation Chimera / growth & development
  • Transplantation Chimera / metabolism

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • Reln protein, mouse
  • Serine Endopeptidases