title: Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development.
abstract: The transcription factors Emx2 and Pax6 are expressed in the proliferating zones of the developing rodent neocortex, and gradients of expression interact in specifying caudal and rostral identities. Pax6 is also involved in corticoneurogenesis, being expressed by radial glial progenitors that give rise to cells that also sequentially express Tbr2, NeuroD and Tbr1, genes temporally downstream of Pax6. In this study, using in situ hybridization, we analysed the expression of EMX2, PAX6, TBR2, NEUROD and TBR1 mRNA in the developing human cortex between 8 and 12 postconceptional weeks (PCW). EMX2 mRNA was expressed in the ventricular (VZ) and subventricular zones (SVZ), but also in the cortical plate, unlike in the rodent. However, gradients of expression were similar to that of the rodent at all ages studied. PAX6 mRNA expression was limited to the VZ and SVZ. At 8 PCW, PAX6 was highly expressed rostrally but less so caudally, as has been seen in the rodent, however this gradient disappeared early in corticogenesis, by 9 PCW. There was less restricted compartment-specific expression of TBR2, NEUROD and TBR1 mRNA than in the rodent, where the gradients of expression were similar to that of PAX6 prior to 9 PCW. The gradient disappeared for TBR2 by 10 PCW, and for NEUROD and TBR1 by 12 PCW. These data support recent reports that EMX2 but not PAX6 is more directly involved in arealization, highlighting that analysis of human development allows better spatio-temporal resolution than studies in rodents.
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: Nadhim
authors.initials: N
authors.lastname: Bayatti
authors.forename: Subrot
authors.initials: S
authors.lastname: Sarma
authors.forename: Christopher
authors.initials: C
authors.lastname: Shaw
authors.forename: Janet A
authors.initials: JA
authors.lastname: Eyre
authors.forename: Demetrius A
authors.initials: DA
authors.lastname: Vouyiouklis
authors.forename: Susan
authors.initials: S
authors.lastname: Lindsay
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Clowry
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002465:Cell Movement / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000037:antagonists & inhibitors; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D012377:Rodentia / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005136:Eye Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C093970:NEUROD1 protein, human; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse; C000605733:Pax6 protein, rat; C493170:TRIB1 protein, human; C523519:Trb1 protein, mouse; C489044:TRIB2 protein, human