Skip to main content
Article thumbnail
Location of Repository

Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development

By Nadhim Bayatti, Subrot Sarma, Christopher Shaw, Janet A Eyre, Demetrius A Vouyiouklis, Susan Lindsay and Gavin J Clowry

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

Topics: Molecular And Developmental Neuroscience
Publisher: Blackwell Publishing Ltd
OAI identifier: oai:pubmedcentral.nih.gov:2675014
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (2004). 3 dimensional modelling of early human brain development using optical projection tomography.
    2. (2005). 3D modelling, gene expression mapping and post-mapping image analysis in the developing human brain.
    3. (2008). A Molecular Neuroanatomical Study of the developing human neocortex from 8 to 17 postconceptional weeks revealing the early differentiation of the subplate and subventricular zone.
    4. (2008). ª The Authors
    5. (2005). Anatomical and gene expression mapping of the ventral pallium in a three-dimensional model of developing human brain.
    6. (2003). Beyond laminar fate: toward a molecular classification of cortical projection ⁄ pyramidal neurons.
    7. (2003). Constructing the mammalian neocortex: the role of intrinsic factors.
    8. (2007). Controlled overexpression of Pax6 in vivo negatively autoregulates the Pax6 locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealization.
    9. (1984). Correlation of fetal age and measurements between 10 and 26 weeks of gestation.
    10. (2002). Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2, and Pax6 mutant mice: evidence that cortical and thalamic axons interact and guide each other.
    11. (1990). Developmental history of the transient subplate zone in the visual and somatosensory cortex of the macaque monkey and human brain.
    12. (2006). Effects of Emx2 inactivation on the gene expression profile of neural precursors.
    13. (2000). Embryonic and early fetal development of the human neocortex.
    14. (2000). Emx homeogenes and mouse brain development.
    15. (1996). Emx1 and Emx2 show different patterns of expression during proliferation and differentiation of the developing cerebral cortex in the mouse.
    16. (2004). EMX2 regulates sizes and positioning of the primary sensory and motor areas in neocortexbydirectspecificationofcorticalprogenitors.Neuron,43,359–372.
    17. (2002). Emx2: a gene responsible for cortical development, regionalization and area specification.
    18. (1999). Expression pattern of the Tbr2 (Eomesodermin) gene during mouse and chick brain development.
    19. (2006). Gene networks controlling early cerebral cortex arealization.
    20. (1995). How do thalamic axons find their way to the cortex?
    21. (2008). Is Pax6 critical for neurogenesis in the human fetal brain?
    22. (2000). Major events in the development of the forebrain.
    23. (2001). Mechanisms of cerebral cortical patterning in mice and humans.
    24. (2005). Molecular insights into human brain evolution.
    25. (2002). Origin of GABAergic neurons in the human neocortex.
    26. (2002). Patterning centers, regulatory genes and extrinsic mechanisms controlling arealization of the neocortex.
    27. (1991). Pax-6, a murine paired box gene, is expressed in the developing CNS.
    28. (1991). Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region.
    29. (2002). regionalization of the preneuronogenic cortical primordium.
    30. (2002). regulating the specification of areas in the developing neocortex.
    31. (2000). Regulation of area identity in the mammalian neocortex by
    32. (2001). Sensitive nonradioactive detection of mRNA in tissue sections: novel application of the whole-mount in situ hybridization protocol.
    33. (1992). Small eye (Sey): cloning and characterization of the murine homolog of the human aniridia gene.
    34. (1995). T-brain-1: a homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex.
    35. (2005). The cell biology of neurogenesis.
    36. (2003). to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding.
    37. (2006). Transcription factors in glutamatergic neurogenesis: conserved programs in neocortex, cerebellum, and adult hippocampus.
    38. (1992). Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex.
    39. (2002). Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey.
    40. (2005). Ventralized dorsal telencephalic progenitors in Pax6 mutant mice generate GABA interneurons of a lateral ganglionic eminence fate.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.