Reelin and disabled-1 expression in developing and mature human cortical neurons

J Neuropathol Exp Neurol. 2003 Jun;62(6):676-84. doi: 10.1093/jnen/62.6.676.

Abstract

In developing mammalian (mouse) brain, Reelin (Reln) is secreted by the Cajal-Retzius (CR) neurons in the marginal zone, binds apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (Vldlr), and induces the phosphorylation of the downstream cytoplasmic molecule disabled-1 (Dab1) in cortical plate neurons. Although this is a well-characterized signaling pathway in mice, it has not been well defined in human brain. In this paper we examined the expression of RELN, APOER2, VLDLR, and DAB1 in the developing human brain by RT-PCR. We further determined the cellular expression of the proteins RELN and DAB1 in 50 human brains ranging in age from 10 gestational weeks (GW) to 62 years using immunochemistry. We found that the pattern of expression of RELN and DAB1 in the human brain isnot identical to that observed in the mouse brain. In particular, we report the novel finding that human DAB1and RELN are coexpressed in CR neurons during cortical development and in cortical pyramidal neurons after neuronal migration is complete. Thus, in the human brain, the whole RELN signaling pathway is present within selected populations of cortical neurons throughout life. We speculate that RELN and DAB1 coexpression in these neurons is necessary for both normal cortical development and mature function.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / embryology
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / metabolism
  • Child
  • Child, Preschool
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Fetus
  • Humans
  • Immunohistochemistry / methods
  • Infant
  • Kidney / metabolism
  • LDL-Receptor Related Proteins
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • RNA, Messenger / biosynthesis
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Receptors, Lipoprotein / genetics
  • Receptors, Lipoprotein / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Serine Endopeptidases

Substances

  • Cell Adhesion Molecules, Neuronal
  • Dab1 protein, mouse
  • Extracellular Matrix Proteins
  • LDL-Receptor Related Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, LDL
  • Receptors, Lipoprotein
  • VLDL receptor
  • low density lipoprotein receptor-related protein 8
  • Serine Endopeptidases
  • reelin protein