Cajal-Retzius cells in the mouse: transcription factors, neurotransmitters, and birthdays suggest a pallial origin

Brain Res Dev Brain Res. 2003 Mar 14;141(1-2):39-53. doi: 10.1016/s0165-3806(02)00641-7.


Cajal-Retzius cells are reelin-secreting neurons found in the marginal zone of the mammalian cortex during development. Recently, it has been proposed that Cajal-Retzius cells may be generated both early and late in corticogenesis, and may migrate into the cortex from proliferative zones in the subpallium (lateral ganglionic eminence and medial ganglionic eminence) or cortical hem. In the present study, we used reelin as a marker to study the properties of Cajal-Retzius cells, including their likely origins, neurotransmitters, and birthdates. In double labeling experiments, Cajal-Retzius cells (reelin(+)) expressed transcription factors characteristic of pallial neurons (Tbr1 and Emx2), contained high levels of glutamate, were usually calretinin(+), and were born early in corticogenesis, on embryonic days (E)10.5 and E11.5. Tbr1(+) cells in the marginal zone were almost always reelin(+). The first Cajal-Retzius cells (Tbr1(+)/reelin(+)) appeared in the preplate on E10.5. In contrast, interneurons expressed a subpallial transcription factor (Dlx), contained high levels of GABA, were frequently calbindin(+), and were born throughout corticogenesis (from E10.5 to E16.5). Interneurons (Dlx(+)) first appeared in the cortex on E12.5. Our results suggest that the marginal zone contains two main types of neurons: Cajal-Retzius cells derived from the pallium, and migrating interneurons derived from the subpallium.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers
  • Calbindin 2
  • Calbindins
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Differentiation / physiology*
  • Cell Division / physiology*
  • Cell Lineage / physiology*
  • Cell Movement / physiology*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism
  • DNA-Binding Proteins / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Fetus
  • Glutamic Acid / metabolism
  • Homeodomain Proteins / metabolism
  • Interneurons / cytology
  • Interneurons / metabolism
  • Mice
  • Mice, Inbred Strains
  • Nerve Tissue Proteins
  • Neurons / cytology
  • Neurons / metabolism*
  • Neurotransmitter Agents / metabolism
  • Pregnancy
  • Reelin Protein
  • S100 Calcium Binding Protein G / metabolism
  • Serine Endopeptidases
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • T-Box Domain Proteins
  • Transcription Factors / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Biomarkers
  • Calb2 protein, mouse
  • Calbindin 2
  • Calbindins
  • Cell Adhesion Molecules, Neuronal
  • DNA-Binding Proteins
  • Distal-less homeobox proteins
  • Extracellular Matrix Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Reelin Protein
  • S100 Calcium Binding Protein G
  • T-Box Domain Proteins
  • Tbr1 protein, mouse
  • Transcription Factors
  • empty spiracles homeobox proteins
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Reln protein, mouse
  • Serine Endopeptidases