title: Neocortical layer formation of human developing brains and lissencephalies: consideration of layer-specific marker expression.
abstract: 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.
authors.affiliation: Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry, Kodaira, 187-8502, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Sae
authors.initials: S
authors.lastname: Hanai
authors.forename: Sachio
authors.initials: S
authors.lastname: Takashima
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakagawa
authors.forename: Shin
authors.initials: S
authors.lastname: Okazaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Rie
authors.initials: R
authors.lastname: Miyata
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hoshino
authors.forename: Takumi
authors.initials: T
authors.lastname: Akashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hayashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itoh
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D000089662:Doublecortin Protein; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D054082:Lissencephaly / Q000378:metabolism / Q000473:pathology*; D019579:Neocortex / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism
chemical_list: D015415:Biomarkers; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein