Neocortical layer formation of human developing brains and lissencephalies: consideration of layer-specific marker expression

Cereb Cortex. 2011 Mar;21(3):588-96. doi: 10.1093/cercor/bhq125. Epub 2010 Jul 12.


To investigate layer-specific molecule expression in human developing neocortices, we performed immunohistochemistry of the layer-specific markers (TBR1, FOXP1, SATB2, OTX1, CUTL1, and CTIP2), using frontal neocortices of the dorsolateral precentral gyri of 16 normal controls, aged 19 gestational weeks to 1 year old, lissencephalies of 3 Miller-Dieker syndrome (MDS) cases, 2 X-linked lissencephaly with abnormal genitalia (XLAG) cases, and 4 Fukuyama-type congenital muscular dystrophy (FCMD) cases. In the fetal period, we observed SATB2+ cells in layers II-IV, CUTL1+ cells in layers II-V, FOXP1+ cells in layer V, OTX1+ cells in layers II or V, and CTIP2+ and TBR1+ cells in layers V and VI. SATB2+ and CUTL1+ cells appeared until 3 months of age, but the other markers disappeared after birth. Neocortices of MDS and XLAG infants revealed SATB2+, CUTL1+, FOXP1+, and TBR1+ cells diffusely located in the upper layers. In fetal FCMD neocortex, neurons labeled with the layer-specific markers located over the glia limitans. The present study provided new knowledge indicating that the expression pattern of these markers in the developing human neocortex was similar to those in mice. Various lissencephalies revealed abnormal layer formation by random migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis*
  • Doublecortin Protein
  • Fetus
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Lissencephaly / metabolism
  • Lissencephaly / pathology*
  • Neocortex / cytology*
  • Neocortex / growth & development
  • Neocortex / metabolism


  • Biomarkers
  • Dcx protein, mouse
  • Doublecortin Protein