Developmental Markers Expressed in Neocortical Layers Are Differentially Exhibited in Olfactory Cortex

PLoS One. 2015 Sep 25;10(9):e0138541. doi: 10.1371/journal.pone.0138541. eCollection 2015.

Abstract

Neurons in the cerebral cortex stratify on the basis of their time of origin, axonal terminations and the molecular identities assigned during early development. Olfactory cortices share many feature with the neocortex, including clear lamination and similar cell types. The present study demonstrates that the markers differentially expressed in the projection neurons of the cerebral cortex are also found in olfactory areas. Three of the four regions examined (pars principalis of the anterior olfactory nucleus: AONpP, anterior and posterior piriform cortices: APC, PPC, and the olfactory tubercle) expressed transcription factors found in deep or superficial neurons in the developing neocortex, though large differences were found between areas. For example, while the AONpP, APC and PPC all broadly expressed the deep cortical marker CTIP2, NOR1 (NR4a3) levels were higher in AONpP and DAARP-32 was more prevalent in the APC and PPC. Similar findings were encountered for superficial cortical markers: all three regions broadly expressed CUX1, but CART was only observed in the APC and PPC. Furthermore, regional variations were observed even within single structures (e.g., NOR1 was found primarily in in the dorsal region of AONpP and CART expression was observed in a discrete band in the middle of layer 2 of both the APC and PPC). Experiments using the mitotic marker EDU verified that the olfactory cortices and neocortex share similar patterns of neuronal production: olfactory cells that express markers found in the deep neocortex are produced earlier than those that express superficial makers. Projection neurons were filled by retrograde tracers injected into the olfactory bulb to see if olfactory neurons with deep and superficial markers had different axonal targets. Unlike the cerebral cortex, no specificity was observed: neurons with each of the transcription factors examined were found to be labelled. Together the results indicate that olfactory cortices are complex: they differ from each other and each is formed from a variable mosaic of neurons. The results suggest that the olfactory cortices are not merely a remnant architype of the primordial forebrain but varied and independent regions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Biomarkers / metabolism*
  • Brain Mapping
  • DNA-Binding Proteins / metabolism
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Inbred C57BL
  • Neocortex / embryology
  • Neocortex / growth & development
  • Neocortex / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Olfactory Bulb / embryology
  • Olfactory Bulb / growth & development
  • Olfactory Bulb / metabolism
  • Olfactory Cortex / embryology
  • Olfactory Cortex / growth & development
  • Olfactory Cortex / metabolism*
  • Olfactory Pathways / physiology
  • Pregnancy
  • Receptors, Steroid / metabolism
  • Receptors, Thyroid Hormone / metabolism
  • Repressor Proteins / metabolism
  • Tissue Distribution
  • Tumor Suppressor Proteins / metabolism

Substances

  • Bcl11b protein, mouse
  • Biomarkers
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Nr4a3 protein, mouse
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • cocaine- and amphetamine-regulated transcript protein