Retinoic acid delineates the topography of neuronal plasticity in postnatal cerebral cortex

Eur J Neurosci. 2006 Jul;24(2):329-40. doi: 10.1111/j.1460-9568.2006.04934.x. Epub 2006 Jul 12.


Retinoic acid is well recognized to promote neuronal differentiation in the embryonic nervous system, but how it influences the postnatal cerebral cortex remains largely unknown. The domain of highest retinoic acid actions in the cortex of the mouse constricts postnatally to a narrow band that includes the dorsal visual stream and the attentional and executive networks. This band of cortex, which is distinguished by the retinoic acid-synthesizing enzyme RALDH3, exhibits signs of delayed maturation and enhanced plasticity compared to the surrounding cortex, as indicated by suppression of parvalbumin, neurofilament, cytochrome oxidase and perineuronal net maturation, and persistence of the embryonic, polysialated form of the neural cell-adhesion molecule PSA-NCAM. During the first postnatal week, the RALDH3-expressing territory translocates in the caudal cortex from the medial limbic lobe to the adjacent neocortex. This topographical shift requires the neurotrophin NT-3 because in mice lacking neuronal NT-3 the RALDH3 enzyme maintains its early postnatal pattern up to adulthood. In the NT-3-null mutants, expression of the markers, whose topography colocalizes with RALDH3 in the normal cortex, matches the abnormal RALDH3 pattern. This indicates that the uneven retinoic acid distribution serves a role in patterning the maturation and to some extent function of the normal postnatal cerebral cortex.

Publication types

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

MeSH terms

  • Aldehyde Oxidoreductases / genetics
  • Aldehyde Oxidoreductases / metabolism*
  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Cell Differentiation / physiology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / metabolism*
  • Electron Transport Complex IV / metabolism
  • Gene Expression Regulation, Developmental / physiology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neural Pathways / cytology
  • Neural Pathways / growth & development
  • Neural Pathways / metabolism
  • Neurofilament Proteins / metabolism
  • Neuronal Plasticity / physiology*
  • Neurons / cytology
  • Neurons / metabolism*
  • Neurotrophin 3 / genetics
  • Parvalbumins / metabolism
  • Protein Transport / physiology
  • Retinal Dehydrogenase
  • Sialic Acids / metabolism
  • Tretinoin / metabolism*


  • Biomarkers
  • Neural Cell Adhesion Molecule L1
  • Neurofilament Proteins
  • Neurotrophin 3
  • Parvalbumins
  • Sialic Acids
  • polysialyl neural cell adhesion molecule
  • Tretinoin
  • Aldehyde Oxidoreductases
  • Retinal Dehydrogenase
  • retinaldehyde dehydrogenase 3, mouse
  • Electron Transport Complex IV